cAMP-dependent protein kinase catalytic subunit alpha

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

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

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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.

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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. Nucleus. Note= Translocates into the nucleus (monomeric catalytic subunit). The inactive holoenzyme is found in the cytoplasm.
Tissue specificity	Ubiquitously expressed in mammalian tissues.
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-3' (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.

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Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Nucleotide-binding cAMP
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	mesoderm formation Inferred from sequence or structural similarity. Source: AgBase protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW neuromuscular junction Inferred from sequence or structural similarity. Source: AgBase nucleus Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro cAMP-dependent protein kinase activity Inferred from electronic annotation. Source: EC protein binding Inferred from sequence or structural similarity. Source: AgBase
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

Removed

Chain

2 – 351

350

cAMP-dependent protein kinase catalytic subunit alpha

PRO_0000086049

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 By similarity

Modified residue

140

1

Phosphoserine By similarity

Modified residue

196

1

Phosphothreonine By similarity

Modified residue

198

1

Phosphothreonine

Modified residue

202

1

Phosphothreonine By similarity

Modified residue

339

1

Phosphoserine

Lipidation

2

1

N-myristoyl glycine

Experimental info

Mutagenesis

3

1

N → D: No myristoylation

Sequence conflict

202

1

T → N AA sequence Ref.4

Sequence conflict

204

1

E → Q AA sequence Ref.4

Sequence conflict

206

1

L → S AA sequence Ref.4

Sequence conflict

287

1

N → D Ref.2 Ref.3

Secondary structure

1

.

351

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P00517-1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 59DDD227D2DEEE5D
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FASTA

351

40,620

        10         20         30         40         50         60 
MGNAAAAKKG SEQESVKEFL AKAKEDFLKK WENPAQNTAH LDQFERIKTL GTGSFGRVML 

        70         80         90        100        110        120 
VKHMETGNHY 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 NEKCGKEFSE F

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References

[1]	"Cloning of the C alpha catalytic subunit of the bovine cAMP-dependent protein kinase." Wiemann S., Kinzel V., Pyerin W. Biochim. Biophys. Acta 1171:93-96(1992) [PubMed: 1420367] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.
[2]	"Complete amino acid sequence of the catalytic subunit of bovine cardiac muscle cyclic AMP-dependent protein kinase." Shoji S., Parmelee D.C., Wade R.D., Kumar S., Ericsson L.H., Walsh K.A., Neurath H., Lonh G.L., Demaille J.G., Fischer E.H., Titani K. Proc. Natl. Acad. Sci. U.S.A. 78:848-851(1981) [PubMed: 6262777] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-351.
[3]	"Amino acid sequence of the catalytic subunit of bovine type II adenosine cyclic 3',5'-phosphate dependent protein kinase." Shoji S., Ericsson L.H., Walsh K.A., Fischer E.H., Titani K. Biochemistry 22:3702-3709(1983) [PubMed: 6311252] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-351.
[4]	"Modification of the catalytic subunit of bovine heart cAMP-dependent protein kinase with affinity labels related to peptide substrates." Bramson H.N., Thomas N., Matsueda R., Nelson N.C., Taylor S.S., Kaiser E.T. J. Biol. Chem. 257:10575-10581(1982) [PubMed: 6286662] [Abstract] Cited for: PROTEIN SEQUENCE OF 196-214, ACTIVE SITE.
[5]	"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, MUTAGENESIS OF ASN-3, DEAMIDATION AT ASN-3.
[6]	"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: 10684253] [Abstract] Cited for: DEAMIDATION AT ASN-3, SUBCELLULAR LOCATION.
[7]	"The amino terminus of PKA catalytic subunit- a site for introduction of posttranslational heterogeneities by deamidation: D-Asp2 and D-isoAsp2 containing isozymes." Kinzel V., Koenig N., Pipkorn R., Bossemeyer D., Lehmann W.D. Protein Sci. 9:2269-2277(2000) [PubMed: 11152138] [Abstract] Cited for: DEAMIDATION AT ASN-3, CHARACTERIZATION OF ASP-3 ISOMERS.
[8]	"Crystal structures of catalytic subunit of cAMP-dependent protein kinase in complex with isoquinolinesulfonyl protein kinase inhibitors H7, H8, and H89. Structural implications for selectivity." Engh R.A., Girod A., Kinzel V., Huber R., Bossemeyer D. J. Biol. Chem. 271:26157-26164(1996) [PubMed: 8824261] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[9]	"Staurosporine-induced conformational changes of cAMP-dependent protein kinase catalytic subunit explain inhibitory potential." Prade L., Engh R.A., Girod A., Kinzel V., Huber R., Bossemeyer D. Structure 5:1627-1637(1997) [PubMed: 9438863] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
+	Additional computationally mapped references.

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Cross-references

Sequence databases

X67154 mRNA. Translation: CAA47627.1.

PIR

OKBO2C. S27159.

RefSeq

NP_777009.1.

UniGene

Bt.4420

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KMU	model	-	C	9-351	[»]
1KMW	model	-	C	9-351	[»]
1Q24	X-ray	2.60	A	1-351	[»]
1Q61	X-ray	2.10	A	1-351	[»]
1Q62	X-ray	2.30	A	1-351	[»]
1Q8T	X-ray	2.00	A	1-351	[»]
1Q8U	X-ray	1.90	A	1-351	[»]
1Q8W	X-ray	2.20	A	1-351	[»]
1SMH	X-ray	2.04	A	1-351	[»]
1STC	X-ray	2.30	E	1-351	[»]
1SVE	X-ray	2.49	A	2-351	[»]
1SVG	X-ray	2.02	A	2-351	[»]
1SVH	X-ray	2.30	A	2-351	[»]
1SZM	X-ray	2.50	A/B	1-351	[»]
1VEB	X-ray	2.89	A	2-351	[»]
1XH4	X-ray	2.45	A	1-351	[»]
1XH5	X-ray	2.05	A	1-351	[»]
1XH6	X-ray	1.90	A	1-351	[»]
1XH7	X-ray	2.47	A	1-351	[»]
1XH8	X-ray	1.60	A	1-351	[»]
1XH9	X-ray	1.64	A	1-351	[»]
1XHA	X-ray	2.46	A	1-351	[»]
1YDR	X-ray	2.20	E	1-351	[»]
1YDS	X-ray	2.20	E	1-351	[»]
1YDT	X-ray	2.30	E	1-351	[»]
2C1A	X-ray	1.95	A	1-351	[»]
2C1B	X-ray	2.00	A	1-351	[»]
2F7E	X-ray	2.00	E	1-351	[»]
2F7X	X-ray	1.90	E	1-351	[»]
2F7Z	X-ray	3.00	E	1-351	[»]
2GFC	X-ray	1.87	A	2-351	[»]
2GNF	X-ray	2.28	A	2-351	[»]
2GNG	X-ray	1.87	A	1-351	[»]
2GNH	X-ray	2.05	A	2-351	[»]
2GNI	X-ray	2.27	A	2-351	[»]
2GNJ	X-ray	2.28	A	1-351	[»]
2GNL	X-ray	2.60	A	1-351	[»]
2JDS	X-ray	2.00	A	1-351	[»]
2JDT	X-ray	2.15	A	1-351	[»]
2JDV	X-ray	2.08	A	1-351	[»]
2OH0	X-ray	2.20	E	1-351	[»]
2OJF	X-ray	2.10	E	1-351	[»]
2UVX	X-ray	2.00	A	1-351	[»]
2UVY	X-ray	1.95	A	1-351	[»]
2UVZ	X-ray	1.94	A	1-351	[»]
2UW0	X-ray	2.00	A	1-351	[»]
2UW3	X-ray	2.19	A	1-351	[»]
2UW4	X-ray	2.00	A	1-351	[»]
2UW5	X-ray	2.14	A	1-351	[»]
2UW6	X-ray	2.23	A	1-351	[»]
2UW7	X-ray	2.10	A	1-351	[»]
2UW8	X-ray	2.00	A	1-351	[»]
2UZT	X-ray	2.10	A	16-351	[»]
2UZU	X-ray	2.40	E	16-351	[»]
2UZV	X-ray	2.50	A	16-351	[»]
2UZW	X-ray	2.20	E	16-351	[»]
2VNW	X-ray	2.09	A	1-351	[»]
2VNY	X-ray	1.96	A

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases