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P68181 (KAPCB_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
cAMP-dependent protein kinase catalytic subunit beta

Short name=PKA C-beta
EC=2.7.11.11
Gene names
Name:Prkacb
Synonyms:Pkacb
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length351 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. 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. Ref.5

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. The cAMP-dependent protein kinase catalytic subunit binds PJA2 By similarity.

Subcellular location

Cytoplasm By similarity. Cell membrane 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 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. Ref.5

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 componentCell membrane
Cytoplasm
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   LigandATP-binding
cAMP
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMLipoprotein
Myristate
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-modulating G-protein coupled receptor signaling pathway

Traceable author statement Ref.5. Source: UniProtKB

negative regulation of meiotic cell cycle

Inferred from electronic annotation. Source: Ensembl

negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning

Inferred from genetic interaction PubMed 22007132. Source: MGI

neural tube closure

Inferred from genetic interaction PubMed 22007132. Source: MGI

protein phosphorylation

Inferred from direct assay Ref.5. Source: UniProtKB

regulation of protein processing

Inferred from genetic interaction PubMed 22007132. Source: MGI

response to clozapine

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcAMP-dependent protein kinase complex

Traceable author statement Ref.5. Source: UniProtKB

centrosome

Inferred from electronic annotation. Source: Ensembl

ciliary base

Inferred from direct assay PubMed 22007132. Source: MGI

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from direct assay Ref.5. Source: UniProtKB

cAMP-dependent protein kinase activity

Inferred from direct assay Ref.5. Source: UniProtKB

magnesium ion binding

Inferred from direct assay Ref.5. 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:
     2-13: 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:
     2-12: Missing.
     13-16: VESV → MGLL
Isoform 4 (identifier: P68181-4)

The sequence of this isoform differs from the canonical sequence as follows:
     2-16: GNTAIAKKGSEVESV → MAAHKELSSG...EHTASWDKSM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 351350cAMP-dependent protein kinase catalytic subunit beta
PRO_0000086061

Regions

Domain44 – 298255Protein kinase
Domain299 – 35153AGC-kinase C-terminal
Nucleotide binding50 – 589ATP By similarity

Sites

Active site1671Proton acceptor By similarity
Binding site731ATP By similarity

Amino acid modifications

Modified residue31Deamidated asparagine By similarity
Modified residue111Phosphoserine By similarity
Modified residue491Phosphothreonine By similarity
Modified residue691Phosphotyrosine Ref.7
Modified residue1401Phosphoserine By similarity
Modified residue1961Phosphothreonine By similarity
Modified residue1981Phosphothreonine By similarity
Modified residue2021Phosphothreonine By similarity
Modified residue3311Phosphotyrosine By similarity
Modified residue3391Phosphoserine By similarity
Lipidation21N-myristoyl glycine Ref.5

Natural variations

Alternative sequence2 – 1615GNTAI…EVESV → MAAHKELSSGQHSGTPTALQ KLEGFASRLFHRHSRGTAQE HRAALEDDGLRASEHTASWD KSM in isoform 4.
VSP_017376
Alternative sequence2 – 1312Missing in isoform 2.
VSP_017373
Alternative sequence2 – 1211Missing in isoform 3.
VSP_017372
Alternative sequence13 – 164VESV → MGLL in isoform 3.
VSP_017375
Alternative sequence14 – 152ES → MN in isoform 2.
VSP_017374

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Beta1) [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: EBAC9B8041DF9F47

FASTA35140,708
        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 

« Hide

Isoform 2 (Beta2) [UniParc].

Checksum: 358F1764027B55F5
Show »

FASTA33939,581
Isoform 3 (Beta3) [UniParc].

Checksum: 3EC91AF8D1418BB7
Show »

FASTA34039,651
Isoform 4 [UniParc].

Checksum: 36FF9CACFDA225BE
Show »

FASTA39946,145

References

« Hide '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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-69, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS17906.1. [P68181-1]
CCDS51090.1. [P68181-2]
CCDS51091.1. [P68181-3]
CCDS51092.1. [P68181-4]
PIROKMSCB. A24596.
RefSeqNP_001157670.1. NM_001164198.1.
NP_001157671.1. NM_001164199.1.
NP_001157672.1. NM_001164200.1.
NP_035230.1. NM_011100.4. [P68181-1]
UniGeneMm.16766.

3D structure databases

ProteinModelPortalP68181.
SMRP68181. Positions 15-351.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202193. 2 interactions.
IntActP68181. 5 interactions.
MINTMINT-4099395.

Chemistry

BindingDBP68181.

PTM databases

PhosphoSiteP68181.

Proteomic databases

PaxDbP68181.
PRIDEP68181.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000005164; ENSMUSP00000005164; ENSMUSG00000005034.
ENSMUST00000102515; ENSMUSP00000099573; ENSMUSG00000005034. [P68181-1]
ENSMUST00000106137; ENSMUSP00000101743; ENSMUSG00000005034.
ENSMUST00000106138; ENSMUSP00000101744; ENSMUSG00000005034.
GeneID18749.
KEGGmmu:18749.
UCSCuc008rrs.2. mouse. [P68181-2]
uc008rrt.2. mouse. [P68181-3]
uc008rru.1. mouse. [P68181-4]
uc008rrv.2. mouse. [P68181-1]

Organism-specific databases

CTD5567.
MGIMGI:97594. Prkacb.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00550000074358.
HOGENOMHOG000233033.
HOVERGENHBG108317.
KOK04345.
OMAGKEFCEF.
OrthoDBEOG7VX8WD.
PhylomeDBP68181.
TreeFamTF313399.

Enzyme and pathway databases

ReactomeREACT_188937. Metabolism.

Gene expression databases

ArrayExpressP68181.
BgeeP68181.
CleanExMM_PRKACB.
GenevestigatorP68181.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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]
ProtoNetSearch...

Other

NextBio294913.
PROP68181.
SOURCESearch...

Entry information

Entry nameKAPCB_MOUSE
AccessionPrimary (citable) accession number: P68181
Secondary accession number(s): P05206 expand/collapse secondary AC list , Q3TQH5, Q3UDD0, Q3UTH5
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot