P05131 (KAPCB_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:

PRKACB

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

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	Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, and differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. 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 By similarity.
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. The cAMP-dependent protein kinase catalytic subunit binds PJA2 By similarity.
Subcellular location	Cytoplasm. Cell membrane By similarity. Nucleus. Note: Translocates into the nucleus (monomeric catalytic subunit). The inactive holoenzyme is found in the cytoplasm. Ref.4
Tissue specificity	Isoform 2 is mainly expressed in heart and brain. Ref.2
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	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding cAMP
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Lipoprotein Myristate Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular component	cytoplasm 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...

Alternative products

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

Note: N-terminal differences in alternatively spliced products could be involved in regulation such as alternative targeting.

Isoform 1 (identifier: P05131-1)

Also known as: Beta-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: P05131-2)

Also known as: Beta-2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: MGNAATAKKGSEVESV → MAAYREVPCN...EHTALWDRSM

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.3
	Chain	2 – 351	350	cAMP-dependent protein kinase catalytic subunit beta		PRO_0000086057
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 Ref.3 Ref.4 Ref.5
	Modified residue	198	1	Phosphothreonine By similarity
	Modified residue	267	1	N6-acetyllysine By similarity
	Modified residue	339	1	Phosphoserine By similarity
	Lipidation	2	1	N-myristoyl glycine Ref.3
Natural variations
	Alternative sequence	1 – 16	16	MGNAA…EVESV → MAAYREVPCNQYTGTTALQK LEGFASRLFHRHSKGTAHDQ KTALENDSLHFSEHTALWDR SM in isoform 2.		VSP_031246

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Beta-1) [UniParc]. Last modified January 23, 2007. Version 2. Checksum: C84D84C2722C9F0C	FASTA	351	40,594
	10 20 30 40 50 60 MGNAATAKKG SEVESVKEFL AKAKEDFLKK WENPAPNNAG LEDFERKKTL GTGSFGRVML 70 80 90 100 110 120 VKHKATEQYY AMKILDKQKV VKLKQIEHTL NEKRILQAVN FPFLVRLEYA FKDNSNLYMV 130 140 150 160 170 180 MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ IVLTFEYLHS LDLIYRDLKP ENLLIDHQGY 190 200 210 220 230 240 IQVTDFGFAK RVKGRTWTLC GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF 250 260 270 280 290 300 ADQPIQIYEK IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVS DIKTHKWFAT 310 320 330 340 350 TDWIAIYQRK VEAPFIPKFR GSGDTSNFDD YEEEDIRVSI TEKCGKEFCE F
	Isoform 2 (Beta-2) [UniParc] [UniParc]. Checksum: 7F87EF506C32FE29	FASTA	397	46,108
	10 20 30 40 50 60 MAAYREVPCN QYTGTTALQK LEGFASRLFH RHSKGTAHDQ KTALENDSLH FSEHTALWDR 70 80 90 100 110 120 SMKEFLAKAK EDFLKKWENP APNNAGLEDF ERKKTLGTGS FGRVMLVKHK ATEQYYAMKI 130 140 150 160 170 180 LDKQKVVKLK QIEHTLNEKR ILQAVNFPFL VRLEYAFKDN SNLYMVMEYV PGGEMFSHLR 190 200 210 220 230 240 RIGRFSEPHA RFYAAQIVLT FEYLHSLDLI YRDLKPENLL IDHQGYIQVT DFGFAKRVKG 250 260 270 280 290 300 RTWTLCGTPE YLAPEIILSK GYNKAVDWWA LGVLIYEMAA GYPPFFADQP IQIYEKIVSG 310 320 330 340 350 360 KVRFPSHFSS DLKDLLRNLL QVDLTKRFGN LKNGVSDIKT HKWFATTDWI AIYQRKVEAP 370 380 390 FIPKFRGSGD TSNFDDYEEE DIRVSITEKC GKEFCEF

References

[1]	"A cloned bovine cDNA encodes an alternate form of the catalytic subunit of cAMP-dependent protein kinase." Showers M.O., Maurer R.A. J. Biol. Chem. 261:16288-16291(1986) [PubMed: 3023347] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Isoform C beta 2, an unusual form of the bovine catalytic subunit of cAMP-dependent protein kinase." Wiemann S., Kinzel V., Pyerin W. J. Biol. Chem. 266:5140-5146(1991) [PubMed: 2002051] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY. Tissue: Heart.
[3]	"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, MYRISTOYLATION AT GLY-2, DEAMIDATION AT ASN-3.
[4]	"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.
[5]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J02647 mRNA. Translation: AAA30707.1. M60482 mRNA. Translation: AAA30424.1.
IPI	IPI00696539. IPI01027991.
PIR	OKBOB2. A23716. OKBOB1. A25334.
RefSeq	NP_777010.1. NM_174585.2.
UniGene	Bt.391.
3D structure databases
ProteinModelPortal	P05131.
SMR	P05131. Positions 14-351.
ModBase	Search...
Protein-protein interaction databases
IntAct	P05131. 27 interactions.
STRING	P05131.
Proteomic databases
PRIDE	P05131.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSBTAT00000044032; ENSBTAP00000041551; ENSBTAG00000011953. ENSBTAT00000050033; ENSBTAP00000046803; ENSBTAG00000011953.
GeneID	282323.
KEGG	bta:282323.
Organism-specific databases
CTD	5567.
Phylogenomic databases
GeneTree	ENSGT00550000074358.
HOVERGEN	HBG108317.
InParanoid	P05131.
PhylomeDB	P05131.
Enzyme and pathway databases
BRENDA	2.7.11.11. 908.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K04345.
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...

Entry information

Entry name

KAPCB_BOVIN

Accession

Primary (citable) accession number: P05131
Secondary accession number(s): P24256

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	November 16, 2011
This is version 116 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program