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Protein

cAMP-dependent protein kinase catalytic subunit beta

Gene

PRKACB

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Activated by cAMP.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei73 – 731ATPPROSITE-ProRule annotation
Active sitei167 – 1671Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi50 – 589ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, cAMP, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.11. 908.
ReactomeiR-BTA-163615. PKA activation.
R-BTA-164378. PKA activation in glucagon signalling.
R-BTA-180024. DARPP-32 events.
R-BTA-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-BTA-392517. Rap1 signalling.
R-BTA-422356. Regulation of insulin secretion.
R-BTA-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-BTA-442720. CREB phosphorylation through the activation of Adenylate Cyclase.
R-BTA-5610785. GLI3 is processed to GLI3R by the proteasome.
R-BTA-5610787. Hedgehog 'off' state.
R-BTA-5621575. CD209 (DC-SIGN) signaling.
R-BTA-5687128. MAPK6/MAPK4 signaling.
R-BTA-983231. Factors involved in megakaryocyte development and platelet production.

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-dependent protein kinase catalytic subunit beta (EC:2.7.11.11)
Short name:
PKA C-beta
Gene namesi
Name:PRKACB
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 3

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2111446.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 351350cAMP-dependent protein kinase catalytic subunit betaPRO_0000086057Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication
Modified residuei3 – 31Deamidated asparagine; partial3 Publications
Modified residuei11 – 111PhosphoserineBy similarity
Modified residuei49 – 491PhosphothreonineBy similarity
Modified residuei69 – 691PhosphotyrosineBy similarity
Modified residuei140 – 1401PhosphoserineBy similarity
Modified residuei196 – 1961PhosphothreonineBy similarity
Modified residuei198 – 1981PhosphothreonineBy similarity
Modified residuei202 – 2021PhosphothreonineBy similarity
Modified residuei322 – 3221PhosphoserineBy similarity
Modified residuei331 – 3311PhosphotyrosineBy similarity
Modified residuei339 – 3391PhosphoserineBy similarity

Post-translational modificationi

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.3 Publications

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

PaxDbiP05131.
PRIDEiP05131.

Expressioni

Tissue specificityi

Isoform 2 is mainly expressed in heart and brain.1 Publication

Gene expression databases

ExpressionAtlasiP05131. baseline and differential.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

BioGridi159585. 26 interactions.
IntActiP05131. 27 interactions.
STRINGi9913.ENSBTAP00000046803.

Structurei

3D structure databases

ProteinModelPortaliP05131.
SMRiP05131. Positions 14-351.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini44 – 298255Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini299 – 35153AGC-kinase C-terminalAdd
BLAST

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0616. Eukaryota.
ENOG410XPQQ. LUCA.
GeneTreeiENSGT00810000125385.
HOVERGENiHBG108317.
InParanoidiP05131.
KOiK04345.
OMAiGKEFCEF.
OrthoDBiEOG7VX8WD.
TreeFamiTF313399.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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

Isoform 1 (identifier: P05131-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGNAATAKKG SEVESVKEFL AKAKEDFLKK WENPAPNNAG LEDFERKKTL
60 70 80 90 100
GTGSFGRVML VKHKATEQYY AMKILDKQKV VKLKQIEHTL NEKRILQAVN
110 120 130 140 150
FPFLVRLEYA FKDNSNLYMV MEYVPGGEMF SHLRRIGRFS EPHARFYAAQ
160 170 180 190 200
IVLTFEYLHS LDLIYRDLKP ENLLIDHQGY IQVTDFGFAK RVKGRTWTLC
210 220 230 240 250
GTPEYLAPEI ILSKGYNKAV DWWALGVLIY EMAAGYPPFF ADQPIQIYEK
260 270 280 290 300
IVSGKVRFPS HFSSDLKDLL RNLLQVDLTK RFGNLKNGVS DIKTHKWFAT
310 320 330 340 350
TDWIAIYQRK VEAPFIPKFR GSGDTSNFDD YEEEDIRVSI TEKCGKEFCE

F
Length:351
Mass (Da):40,594
Last modified:January 23, 2007 - v2
Checksum:iC84D84C2722C9F0C
GO
Isoform 2 (identifier: P05131-2) [UniParc] [UniParc]FASTAAdd to basket

Also known as: Beta-2

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

Show »
Length:397
Mass (Da):46,108
Checksum:i7F87EF506C32FE29
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1616MGNAA…EVESV → MAAYREVPCNQYTGTTALQK LEGFASRLFHRHSKGTAHDQ KTALENDSLHFSEHTALWDR SM in isoform 2. 1 PublicationVSP_031246Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02647 mRNA. Translation: AAA30707.1.
M60482 mRNA. Translation: AAA30424.1.
PIRiA23716. OKBOB2.
A25334. OKBOB1.
RefSeqiNP_777010.1. NM_174585.3. [P05131-1]
XP_005204430.1. XM_005204373.3. [P05131-2]
UniGeneiBt.391.

Genome annotation databases

EnsembliENSBTAT00000044032; ENSBTAP00000041551; ENSBTAG00000011953. [P05131-1]
ENSBTAT00000050033; ENSBTAP00000046803; ENSBTAG00000011953. [P05131-2]
GeneIDi282323.
KEGGibta:282323.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02647 mRNA. Translation: AAA30707.1.
M60482 mRNA. Translation: AAA30424.1.
PIRiA23716. OKBOB2.
A25334. OKBOB1.
RefSeqiNP_777010.1. NM_174585.3. [P05131-1]
XP_005204430.1. XM_005204373.3. [P05131-2]
UniGeneiBt.391.

3D structure databases

ProteinModelPortaliP05131.
SMRiP05131. Positions 14-351.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi159585. 26 interactions.
IntActiP05131. 27 interactions.
STRINGi9913.ENSBTAP00000046803.

Chemistry

ChEMBLiCHEMBL2111446.

Proteomic databases

PaxDbiP05131.
PRIDEiP05131.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000044032; ENSBTAP00000041551; ENSBTAG00000011953. [P05131-1]
ENSBTAT00000050033; ENSBTAP00000046803; ENSBTAG00000011953. [P05131-2]
GeneIDi282323.
KEGGibta:282323.

Organism-specific databases

CTDi5567.

Phylogenomic databases

eggNOGiKOG0616. Eukaryota.
ENOG410XPQQ. LUCA.
GeneTreeiENSGT00810000125385.
HOVERGENiHBG108317.
InParanoidiP05131.
KOiK04345.
OMAiGKEFCEF.
OrthoDBiEOG7VX8WD.
TreeFamiTF313399.

Enzyme and pathway databases

BRENDAi2.7.11.11. 908.
ReactomeiR-BTA-163615. PKA activation.
R-BTA-164378. PKA activation in glucagon signalling.
R-BTA-180024. DARPP-32 events.
R-BTA-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-BTA-392517. Rap1 signalling.
R-BTA-422356. Regulation of insulin secretion.
R-BTA-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-BTA-442720. CREB phosphorylation through the activation of Adenylate Cyclase.
R-BTA-5610785. GLI3 is processed to GLI3R by the proteasome.
R-BTA-5610787. Hedgehog 'off' state.
R-BTA-5621575. CD209 (DC-SIGN) signaling.
R-BTA-5687128. MAPK6/MAPK4 signaling.
R-BTA-983231. Factors involved in megakaryocyte development and platelet production.

Miscellaneous databases

NextBioi20806120.

Gene expression databases

ExpressionAtlasiP05131. baseline and differential.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. 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]
ProtoNetiSearch...

Publicationsi

  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: DEAMIDATION AT ASN-3, CHARACTERIZATION OF ASP-3 ISOMERS.

Entry informationi

Entry nameiKAPCB_BOVIN
AccessioniPrimary (citable) accession number: P05131
Secondary accession number(s): P24256
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: May 11, 2016
This is version 153 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.