Reviewed, UniProtKB/Swiss-Prot P68181 (KAPCB_MOUSE)

Names and origin

Protein names

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

Gene names

Name:	Prkacb
Synonyms:	Pkacb

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	Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, 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.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
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	CytoplasmBy similarity. NucleusBy similarity. Note= Translocates into the nucleus (monomeric catalytic subunit) By similarity. The inactive holoenzyme is found in the cytoplasm By similarity.
Tissue specificity	Isoform 1 is found in all tissues examined, with the highest expression in the brain and very low levels in the testis. Isoform 2 is strongly expressed in the brain, in the prelimbic and insular cortex. Isoform 3 is also found only in the brain, but at very low levels.
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 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	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
Gene Ontology (GO)
Biological process	G-protein signaling, coupled to cAMP nucleotide second messenger Ref.5 Traceable author statement. Source: UniProtKB protein amino acid phosphorylation Ref.5 Inferred from direct assay. Source: UniProtKB
Cellular component	cAMP-dependent protein kinase complex Ref.5 Traceable author statement. Source: UniProtKB cytosol Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Ref.5 Inferred from direct assay. Source: UniProtKB cAMP-dependent protein kinase activity Ref.5 Inferred from direct assay. Source: UniProtKB magnesium ion binding Ref.5 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P68181-1)

Also known as: Beta1;

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: P68181-2)

Also known as: Beta2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: Missing.
     14-15: ES → MN

Isoform 3 (identifier: P68181-3)

Also known as: Beta3;

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: Missing.
     13-16: VESV → MGLL

Isoform 4 (identifier: P68181-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: MGNTAIAKKGSEVESV → MAAHKELSSG...EHTASWDKSM

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 351	350	cAMP-dependent protein kinase catalytic subunit beta
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 By similarity
	Modified residue	69	1	Phosphotyrosine
	Modified residue	198	1	Phosphothreonine
	Modified residue	339	1	Phosphoserine By similarity
	Lipidation	2	1	N-myristoyl glycine
Natural variations
	Alternative sequence	1 – 16	16	MGNTA…EVESV → MAAHKELSSGQHSGTPTALQ KLEGFASRLFHRHSRGTAQE HRAALEDDGLRASEHTASWD KSM in isoform 4.
	Alternative sequence	1 – 13	13	Missing in isoform 2.
	Alternative sequence	1 – 12	12	Missing in isoform 3.
	Alternative sequence	13 – 16	4	VESV → MGLL in isoform 3.
	Alternative sequence	14 – 15	2	ES → MN in isoform 2.

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Beta1) [UniParc]. Last modified January 23, 2007. Version 2. Checksum: EBAC9B8041DF9F47	FASTA	351	40,708
	10 20 30 40 50 60 MGNTAIAKKG SEVESVKEFL AKAKEDFLRK WENPPPSNAG LEDFERKKTL GTGSFGRVML 70 80 90 100 110 120 VKHKATEQYY AMKILDKQKV VKLKQIEHTL NEKRILQAVE FPFLVRLEYS 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 YEEEEIRVSI TEKCGKEFCE F
	Isoform 2 (Beta2) [UniParc]. Checksum: 346B9D8B775CA4B6		338	39,449
	10 20 30 40 50 60 MNVKEFLAKA KEDFLRKWEN PPPSNAGLED FERKKTLGTG SFGRVMLVKH KATEQYYAMK 70 80 90 100 110 120 ILDKQKVVKL KQIEHTLNEK RILQAVEFPF LVRLEYSFKD NSNLYMVMEY VPGGEMFSHL 130 140 150 160 170 180 RRIGRFSEPH ARFYAAQIVL TFEYLHSLDL IYRDLKPENL LIDHQGYIQV TDFGFAKRVK 190 200 210 220 230 240 GRTWTLCGTP EYLAPEIILS KGYNKAVDWW ALGVLIYEMA AGYPPFFADQ PIQIYEKIVS 250 260 270 280 290 300 GKVRFPSHFS SDLKDLLRNL LQVDLTKRFG NLKNGVSDIK THKWFATTDW IAIYQRKVEA 310 320 330 PFIPKFRGSG DTSNFDDYEE EEIRVSITEK CGKEFCEF
	Isoform 3 (Beta3) [UniParc]. Checksum: 5018FE723E34AC46		339	39,520
	10 20 30 40 50 60 MGLLKEFLAK AKEDFLRKWE NPPPSNAGLE DFERKKTLGT GSFGRVMLVK HKATEQYYAM 70 80 90 100 110 120 KILDKQKVVK LKQIEHTLNE KRILQAVEFP FLVRLEYSFK DNSNLYMVME YVPGGEMFSH 130 140 150 160 170 180 LRRIGRFSEP HARFYAAQIV LTFEYLHSLD LIYRDLKPEN LLIDHQGYIQ VTDFGFAKRV 190 200 210 220 230 240 KGRTWTLCGT PEYLAPEIIL SKGYNKAVDW WALGVLIYEM AAGYPPFFAD QPIQIYEKIV 250 260 270 280 290 300 SGKVRFPSHF SSDLKDLLRN LLQVDLTKRF GNLKNGVSDI KTHKWFATTD WIAIYQRKVE 310 320 330 APFIPKFRGS GDTSNFDDYE EEEIRVSITE KCGKEFCEF
	Isoform 4 [UniParc]. Checksum: E9C32F84ED1FB98B		398	46,014
	10 20 30 40 50 60 MAAHKELSSG QHSGTPTALQ KLEGFASRLF HRHSRGTAQE HRAALEDDGL RASEHTASWD 70 80 90 100 110 120 KSMKEFLAKA KEDFLRKWEN PPPSNAGLED FERKKTLGTG SFGRVMLVKH KATEQYYAMK 130 140 150 160 170 180 ILDKQKVVKL KQIEHTLNEK RILQAVEFPF LVRLEYSFKD NSNLYMVMEY VPGGEMFSHL 190 200 210 220 230 240 RRIGRFSEPH ARFYAAQIVL TFEYLHSLDL IYRDLKPENL LIDHQGYIQV TDFGFAKRVK 250 260 270 280 290 300 GRTWTLCGTP EYLAPEIILS KGYNKAVDWW ALGVLIYEMA AGYPPFFADQ PIQIYEKIVS 310 320 330 340 350 360 GKVRFPSHFS SDLKDLLRNL LQVDLTKRFG NLKNGVSDIK THKWFATTDW IAIYQRKVEA 370 380 390 PFIPKFRGSG DTSNFDDYEE EEIRVSITEK CGKEFCEF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Evidence for a second isoform of the catalytic subunit of cAMP-dependent protein kinase." Uhler M.D., Chrivia J.C., McKnight G.S. J. Biol. Chem. 261:15360-15363(1986) [PubMed: 3023318] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3 AND 4). Strain: C57BL/6J. Tissue: Adrenal gland and Head.
[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: C57BL/6. Tissue: Brain.
[4]	"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] OF 1-15 (ISOFORM 1).
[5]	"Two novel brain-specific splice variants of the murine Cbeta gene of cAMP-dependent protein kinase." Guthrie C.R., Skalhegg B.S., McKnight G.S. J. Biol. Chem. 272:29560-29565(1997) [PubMed: 9368018] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-7 (ISOFORM 2), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-8 (ISOFORM 3), FUNCTION, MYRISTOYLATION AT GLY-2, TISSUE SPECIFICITY.
[6]	"A collection of cDNA clones with specific expression patterns in mouse brain." Kato K. Eur. J. Neurosci. 2:704-711(1990) [PubMed: 12106288] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 281-351. Strain: BALB/c. Tissue: Brain.
[7]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed: 18034455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-69, MASS SPECTROMETRY. Tissue: Brain.
[8]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed: 17114649] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-198, MASS SPECTROMETRY. Tissue: Brain cortex.

Cross-references

Sequence databases
EMBLGenBankDDBJ	J02626 mRNA. Translation: AAA39941.1. AK048319 mRNA. Translation: BAC33301.1. AK139419 mRNA. Translation: BAE24005.1. AK148728 mRNA. Translation: BAE28648.1. AK150122 mRNA. Translation: BAE29323.1. AK150134 mRNA. Translation: BAE29331.1. AK163585 mRNA. Translation: BAE37407.1. BC054533 mRNA. Translation: AAH54533.1. M21096 Genomic DNA. Translation: AAA39938.1. AF022239 Genomic DNA. No translation available. X61434 mRNA. Translation: CAA43676.1.
PIR	OKMSCB. A24596.
RefSeq	NP_035230.1.
UniGene	Mm.16766
3D structure databases
HSSP	HSSP built from PDB template 1CTP based on UniProtKB P36887.
ModBase	Search...
Protein-protein interaction databases
IntAct	P68181.
Genome annotation databases
Ensembl	ENSMUSG00000005034. Mus musculus. [Contig view]
GeneID	18749.
KEGG	mmu:18749.
Organism-specific databases
MGI	MGI:97594. Prkacb.
Phylogenomic databases
HOGENOM	P68181.
HOVERGEN	P68181.
Gene expression databases
ArrayExpress	P68181.
CleanEx	MM_PRKACB.
GermOnline	ENSMUSG00000005034. Mus musculus.
Family and domain databases
InterPro	IPR000961. Pkinase_C. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. 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]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

KAPCB_MOUSE

Accession

Primary (citable) accession number: P68181
Secondary accession number(s): P05206 , Q3TQH5, Q3UDD0, Q3UTH5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	January 23, 2007
Last modified:	July 22, 2008
This is version 52 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)