Reviewed, UniProtKB/Swiss-Prot P05132 (KAPCA_MOUSE)

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
Synonyms:	Pkaca

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

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	Isoform 2 is sperm specific.
Post-translational modification	Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity. Ref.5 Ref.6 Ref.7 Asn-3 is partially deaminated to Asp-3 giving rise to 2 major isoelectric variants, called CB and CA respectively. When myristoylated, Ser-11 is autophosphorylated probably in conjunction with deamidation of Asn-3. Ref.5 Ref.6 Ref.7
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	3D-structure
Gene Ontology (GO)
Biological process	mesoderm formation Inferred from genetic interaction. Source: MGI positive regulation of protein export from nucleus Inferred from mutant phenotype. Source: MGI protein amino acid autophosphorylation Inferred from direct assay. Source: MGI regulation of synaptic transmission Inferred from mutant phenotype. Source: MGI
Cellular component	cytosol Inferred from Experiment. Source: Reactome mitochondrion Inferred from direct assay. Source: MGI neuromuscular junction Inferred from direct assay. Source: MGI nucleoplasm Inferred from Experiment. Source: Reactome plasma membrane Inferred from direct assay. Source: MGI
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW cAMP-dependent protein kinase activity Inferred from Experiment. Source: Reactome protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PRKAR1A	P00514	1	EBI-400564,EBI-1041635	From a different organism.

Alternative products

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

Isoform 1 (identifier: P05132-1)

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: P05132-2)

Also known as: C-alpha-2; C-alpha-S; C(s);

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 351

350

cAMP-dependent protein kinase catalytic subunit alpha

PRO_0000086053

Regions

Domain

44 – 298

255

Protein kinase

Domain

299 – 351

53

AGC-kinase C-terminal

Nucleotide binding

50 – 58

9

ATP

Sites

Active site

167

1

Proton acceptor

Binding site

73

1

ATP

Amino acid modifications

Modified residue

3

1

Deamidated asparagine; partial

Modified residue

11

1

Phosphoserine; by autocatalysis Ref.5

Modified residue

35

1

Phosphoserine Ref.7

Modified residue

49

1

Phosphothreonine By similarity

Modified residue

140

1

Phosphoserine

Modified residue

196

1

Phosphothreonine Ref.6

Modified residue

198

1

Phosphothreonine

Modified residue

202

1

Phosphothreonine By similarity

Modified residue

339

1

Phosphoserine

Lipidation

2

1

N-myristoyl glycine

Natural variations

Alternative sequence

1 – 15

15

MGNAA…SEQES → MASSSND in isoform 2.

VSP_004760

Experimental info

Mutagenesis

198

1

T → D: No phosphorylation by PDPK1.

Sequence conflict

33

1

T → D in AAA39936. Ref.2

Sequence conflict

287

1

N → D in AAA39936. Ref.2

Secondary structure

1

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351

Helix Strand Turn

Details...

Helix

16 – 32

17

Helix

41 – 43

3

Beta strand

44 – 52

9

Beta strand

57 – 63

7

Turn

64 – 66

3

Beta strand

69 – 76

8

Helix

77 – 82

6

Helix

86 – 96

11

Beta strand

107 – 112

6

Beta strand

114 – 122

9

Helix

129 – 136

8

Helix

141 – 160

20

Helix

170 – 172

3

Beta strand

173 – 175

3

Beta strand

181 – 183

3

Helix

203 – 205

3

Helix

208 – 211

4

Helix

219 – 234

16

Helix

244 – 253

10

Helix

264 – 273

10

Turn

278 – 280

3

Turn

286 – 289

4

Helix

290 – 293

4

Helix

296 – 298

3

Helix

303 – 307

5

Turn

345 – 350

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (C-alpha-1) [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 02F85D66EB21A1FA	FASTA	351	40,571
	10 20 30 40 50 60 MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WETPSQNTAQ LDQFDRIKTL GTGSFGRVML 70 80 90 100 110 120 VKHKESGNHY AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVKLEFS FKDNSNLYMV 130 140 150 160 170 180 MEYVAGGEMF 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 (C-alpha-2) (C-alpha-S) (C(s)). Checksum: EC2012B8F9A59DB7	FASTA	343	39,803
	10 20 30 40 50 60 MASSSNDVKE FLAKAKEDFL KKWETPSQNT AQLDQFDRIK TLGTGSFGRV MLVKHKESGN 70 80 90 100 110 120 HYAMKILDKQ KVVKLKQIEH TLNEKRILQA VNFPFLVKLE FSFKDNSNLY MVMEYVAGGE 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

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of genomic clones coding for the C alpha and C beta subunits of mouse cAMP-dependent protein kinase." Chrivia J.C., Uhler M.D., McKnight G.S. J. Biol. Chem. 263:5739-5744(1988) [PubMed: 2833513] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[2]	"Isolation of cDNA clones coding for the catalytic subunit of mouse cAMP-dependent protein kinase." Uhler M.D., Carmichael D.F., Lee D.C., Chrivia J.C., Krebs E.G., McKnight G.S. Proc. Natl. Acad. Sci. U.S.A. 83:1300-1304(1986) [PubMed: 3456589] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: FVB/N-3. Tissue: Mammary tumor.
[4]	"The unique catalytic subunit of sperm cAMP-dependent protein kinase is the product of an alternative C-alpha mRNA expressed specifically in spermatogenic cells." San Agustin J.T., Wilkerson C.G., Witman G.B. Mol. Biol. Cell 11:3031-3044(2000) [PubMed: 10982398] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-153 (ISOFORM 2). Tissue: Testis.
[5]	"Influence of myristoylation, phosphorylation, and deamidation on the structural behavior of the N-terminus of the catalytic subunit of cAMP-dependent protein kinase." Tholey A., Pipkorn R., Bossemeyer D., Kinzel V., Reed J. Biochemistry 40:225-231(2001) [PubMed: 11141074] [Abstract] Cited for: MYRISTOYLATION AT GLY-2, PHOSPHORYLATION AT SER-11, DEAMIDATION AT ASN-3.
[6]	"Phosphoproteomic analysis of the developing mouse brain." Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P. Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed: 15345747] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-196, MASS SPECTROMETRY. Tissue: Brain.
[7]	"Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry." Dai J., Jin W.-H., Sheng Q.-H., Shieh C.-H., Wu J.-R., Zeng R. J. Proteome Res. 6:250-262(2007) [PubMed: 17203969] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, MASS SPECTROMETRY. Tissue: Liver.
[8]	"Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase." Knighton D.R., Zheng J., ten Eyck L.F., Ashford V.A., Xuong N.-H., Taylor S.S., Sowadski J.M. Science 253:407-414(1991) [PubMed: 1862342] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
[9]	"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: 8443157] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF COMPLEX WITH INHIBITOR.
[10]	"Crystal structure of a polyhistidine-tagged recombinant catalytic subunit of cAMP-dependent protein kinase complexed with the peptide inhibitor PKI(5-24) and adenosine." Narayana N., Cox S., Shaltiel S., Taylor S.S., Xuong N. Biochemistry 36:4438-4448(1997) [PubMed: 9109651] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF COMPLEX WITH INHIBITOR.
[11]	"A binary complex of the catalytic subunit of cAMP-dependent protein kinase and adenosine further defines conformational flexibility." Narayana N., Cox S., Nguyen-Huu X., ten Eyck L.F., Taylor S.S. Structure 5:921-935(1997) [PubMed: 9261084] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M19960 , M18240, M18241, M19953, M19954, M19955, M19956, M19957, M19958, M19959 Genomic DNA. Translation: AAA39937.1.
M12303 mRNA. Translation: AAA39936.1.
BC003238 mRNA. Translation: AAH03238.1.
BC054834 mRNA. Translation: AAH54834.1.
AF239743 mRNA. Translation: AAF76425.1.

IPI

IPI00227900.
IPI00230005.

PIR

OKMSCA. A28619.

RefSeq

NP_032880.1.

UniGene

Mm.19111

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1APM	X-ray	2.00	E	2-350	[»]
1ATP	X-ray	2.20	E	2-350	[»]
1BKX	X-ray	2.60	A	2-351	[»]
1BX6	X-ray	2.10	A	2-350	[»]
1FMO	X-ray	2.20	E	2-351	[»]
1J3H	X-ray	2.90	A/B	2-350	[»]
1JBP	X-ray	2.20	E	2-350	[»]
1JLU	X-ray	2.25	E	2-350	[»]
1L3R	X-ray	2.00	E	2-350	[»]
1PVK	model	-	B	16-351	[»]
1RDQ	X-ray	1.26	E	2-350	[»]
1RE8	X-ray	2.10	A	2-350	[»]
1REJ	X-ray	2.20	A	2-350	[»]
1REK	X-ray	2.30	A	2-350	[»]
1SYK	X-ray	2.80	A/B	2-351	[»]
2CPK	X-ray	2.70	E	2-351	[»]
2ERZ	X-ray	2.20	E	1-351	[»]
2QCS	X-ray	2.20	A	2-351	[»]
2QUR	X-ray	2.50	A	2-351	[»]
2QVS	X-ray	2.50	E	2-351	[»]
3FHI	X-ray	2.00	A	2-351	[»]
3FJQ	X-ray	1.60	E	2-351	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:6086N.

IntAct

P05132. 4 interactions.

STRING

P05132.

PTM databases

PhosphoSite

P05132.

Proteomic databases

PRIDE

P05132.

Genome annotation databases

Ensembl

ENSMUST00000005606; ENSMUSP00000005606; ENSMUSG00000005469; Mus musculus. [Genome view]
ENSMUST00000059266; ENSMUSP00000105424; ENSMUSG00000005469; Mus musculus. [Genome view]

GeneID

18747.

KEGG

mmu:18747.

UCSC

uc009mll.1. mouse.

Organism-specific databases

CTD

18747.

MGI

MGI:97592. Prkaca.

Phylogenomic databases

HOGENOM

P05132.

HOVERGEN

P05132.

OMA

GQHFAMK.

Enzyme and pathway databases

BRENDA

2.7.11.11. 244.

Gene expression databases

ArrayExpress

P05132.

Bgee

P05132.

CleanEx

MM_PRKACA.

Genevestigator

P05132.

GermOnline

ENSMUSG00000005469. Mus musculus.

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

P05132.

NextBio

294909.

SOURCE

Search...

Entry information

Entry name

KAPCA_MOUSE

Accession

Primary (citable) accession number: P05132
Secondary accession number(s): Q9JID0

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	November 3, 2009
This is version 135 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)