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Protein

cAMP-dependent protein kinase catalytic subunit beta

Gene

PRKACB

Organism
Homo sapiens (Human)
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, 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.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

Activated by cAMP.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei73ATPPROSITE-ProRule annotation1
Active sitei167Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi50 – 58ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • cAMP-dependent protein kinase activity Source: UniProtKB
  • kinase activity Source: Reactome
  • magnesium ion binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: Reactome
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, cAMP, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.11. 2681.
ReactomeiR-HSA-111931. PKA-mediated phosphorylation of CREB.
R-HSA-163358. PKA-mediated phosphorylation of key metabolic factors.
R-HSA-163560. Triglyceride catabolism.
R-HSA-163615. PKA activation.
R-HSA-164378. PKA activation in glucagon signalling.
R-HSA-180024. DARPP-32 events.
R-HSA-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-HSA-392517. Rap1 signalling.
R-HSA-422356. Regulation of insulin secretion.
R-HSA-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-HSA-4420097. VEGFA-VEGFR2 Pathway.
R-HSA-442720. CREB phosphorylation through the activation of Adenylate Cyclase.
R-HSA-5610780. Degradation of GLI1 by the proteasome.
R-HSA-5610783. Degradation of GLI2 by the proteasome.
R-HSA-5610785. GLI3 is processed to GLI3R by the proteasome.
R-HSA-5610787. Hedgehog 'off' state.
R-HSA-5621575. CD209 (DC-SIGN) signaling.
R-HSA-5687128. MAPK6/MAPK4 signaling.
R-HSA-70171. Glycolysis.
R-HSA-8853659. RET signaling.
R-HSA-8963896. HDL assembly.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SABIO-RKiP22694.
SignaLinkiP22694.
SIGNORiP22694.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000142875.19.
HGNCiHGNC:9381. PRKACB.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi5567.
OpenTargetsiENSG00000142875.
PharmGKBiPA33749.

Chemistry databases

ChEMBLiCHEMBL2918.
DrugBankiDB02482. Phosphonothreonine.
GuidetoPHARMACOLOGYi1477.

Polymorphism and mutation databases

BioMutaiPRKACB.
DMDMi125210.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000860602 – 351cAMP-dependent protein kinase catalytic subunit betaAdd BLAST350

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Modified residuei3Deamidated asparagineBy similarity1
Modified residuei69PhosphotyrosineBy similarity1
Modified residuei322PhosphoserineBy similarity1
Modified residuei339PhosphoserineBy similarity1

Post-translational modificationi

Asn-3 is partially deaminated to Asp giving rise to 2 major isoelectric variants, called CB and CA respectively.By similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein

Proteomic databases

EPDiP22694.
MaxQBiP22694.
PaxDbiP22694.
PeptideAtlasiP22694.
PRIDEiP22694.

PTM databases

iPTMnetiP22694.
PhosphoSitePlusiP22694.
SwissPalmiP22694.

Expressioni

Tissue specificityi

Isoform 1 is most abundant in the brain, with low level expression in kidney. Isoform 2 is predominantly expressed in thymus, spleen and kidney. Isoform 3 and isoform 4 are only expressed in the brain.1 Publication

Gene expression databases

BgeeiENSG00000142875.
ExpressionAtlasiP22694. baseline and differential.
GenevisibleiP22694. HS.

Organism-specific databases

HPAiCAB010363.
HPA029754.
HPA071185.

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

Binary interactionsi

Show more details

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111554. 85 interactors.
IntActiP22694. 46 interactors.
MINTiMINT-1178341.
STRINGi9606.ENSP00000359719.

Chemistry databases

BindingDBiP22694.

Structurei

3D structure databases

ProteinModelPortaliP22694.
SMRiP22694.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 298Protein kinasePROSITE-ProRule annotationAdd BLAST255
Domaini299 – 351AGC-kinase C-terminalAdd BLAST53

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0616. Eukaryota.
ENOG410XPQQ. LUCA.
GeneTreeiENSGT00810000125385.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiP22694.
KOiK04345.
OMAiGKEFCEF.
OrthoDBiEOG091G10O8.
PhylomeDBiP22694.
TreeFamiTF313399.

Family and domain databases

InterProiView protein in InterPro
IPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in 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.

Sequences (10)i

Sequence statusi: Complete.

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

This entry describes 10 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P22694-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MGNAATAKKG SEVESVKEFL AKAKEDFLKK WENPTQNNAG 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 TEKCAKEFGE

F
Length:351
Mass (Da):40,623
Last modified:January 23, 2007 - v2
Checksum:i5C7443FBBA1C9BEC
GO
Isoform 2 (identifier: P22694-2) [UniParc]FASTAAdd to basket
Also known as: Beta2

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

Show »
Length:398
Mass (Da):46,236
Checksum:i49EFAF3E426468FC
GO
Isoform 3 (identifier: P22694-3) [UniParc]FASTAAdd to basket
Also known as: Beta3

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

Note: Incomplete sequence.
Show »
Length:339
Mass (Da):39,477
Checksum:iAD0D54B6EEB01501
GO
Isoform 4 (identifier: P22694-4) [UniParc]FASTAAdd to basket
Also known as: Beta4

The sequence of this isoform differs from the canonical sequence as follows:
     1-13: Missing.
     14-14: E → M

Note: Incomplete sequence.
Show »
Length:338
Mass (Da):39,379
Checksum:iCFB30E746FD025F5
GO
Isoform 5 (identifier: P22694-5) [UniParc]FASTAAdd to basket
Also known as: Beta4ab

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MGNAATAKKGSEVE → MSARKSSDASACSSSEI

Note: Incomplete sequence.
Show »
Length:354
Mass (Da):40,947
Checksum:i7BB4E4E199E5B0B4
GO
Isoform 6 (identifier: P22694-6) [UniParc]FASTAAdd to basket
Also known as: Beta4abc

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MGNAATAKKGSEVES → MSARKSSDASACSSSEISDSF

Show »
Length:357
Mass (Da):41,296
Checksum:iFC923359146B9466
GO
Isoform 7 (identifier: P22694-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MGNAATAKKGSEVE → MGLSRKSSDASACSSSEI

Note: No experimental confirmation available.
Show »
Length:355
Mass (Da):41,046
Checksum:i02D5CA2B459BDDF1
GO
Isoform 8 (identifier: P22694-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     256-257: VR → NF
     258-351: Missing.

Show »
Length:257
Mass (Da):29,696
Checksum:i38FCBB18E1BF2761
GO
Isoform 9 (identifier: P22694-9) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MGNAATAKKGSEVES → MGLSRKSSDASACSSSEISDSF

Note: No experimental confirmation available.
Show »
Length:358
Mass (Da):41,395
Checksum:iB5E2A85075455EBA
GO
Isoform 10 (identifier: P22694-10) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MGNAATAKKGSEVE → MSARKSSDASACSSSEI
     79-111: Missing.

Note: No experimental confirmation available.
Show »
Length:321
Mass (Da):36,979
Checksum:i7FF5EB27D1706E88
GO

Sequence cautioni

The sequence BAD92426 differs from that shown. Reason: Frameshift at position 322.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti80V → G in CAI56774 (Ref. 3) Curated1
Sequence conflicti159H → N in AAH35058 (PubMed:15489334).Curated1
Sequence conflicti163L → I in AAH35058 (PubMed:15489334).Curated1
Sequence conflicti233A → V in CAI56774 (Ref. 3) Curated1
Sequence conflicti261H → N in AAH35058 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040594106R → Q1 PublicationCorresponds to variant dbSNP:rs36117118Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0173641 – 16MGNAA…EVESV → MAAYREPPCNQYTGTTTALQ KLEGFASRLFHRHSKGTAHD QKTALENDSLHFSEHTALWD RSM in isoform 2. 2 PublicationsAdd BLAST16
Alternative sequenceiVSP_0173651 – 15MGNAA…SEVES → MSARKSSDASACSSSEISDS F in isoform 6. 2 PublicationsAdd BLAST15
Alternative sequenceiVSP_0433721 – 15MGNAA…SEVES → MGLSRKSSDASACSSSEISD SF in isoform 9. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_0173661 – 14MGNAA…GSEVE → MSARKSSDASACSSSEI in isoform 5 and isoform 10. 2 PublicationsAdd BLAST14
Alternative sequenceiVSP_0173671 – 14MGNAA…GSEVE → MGLSRKSSDASACSSSEI in isoform 7. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_0173681 – 13Missing in isoform 4. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_0173691 – 12Missing in isoform 3. 2 PublicationsAdd BLAST12
Alternative sequenceiVSP_01737013 – 16VESV → MGLL in isoform 3. 2 Publications4
Alternative sequenceiVSP_01737114E → M in isoform 4. 1 Publication1
Alternative sequenceiVSP_04623879 – 111Missing in isoform 10. 1 PublicationAdd BLAST33
Alternative sequenceiVSP_036556256 – 257VR → NF in isoform 8. 1 Publication2
Alternative sequenceiVSP_036557258 – 351Missing in isoform 8. 1 PublicationAdd BLAST94

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34181 mRNA. Translation: AAA60170.1.
BX537705 mRNA. Translation: CAD97818.1.
BX641026 mRNA. Translation: CAE46017.1.
AB209189 mRNA. Translation: BAD92426.1. Sequence problems.
CR936631 mRNA. Translation: CAI56774.1.
AK091420 mRNA. Translation: BAG52356.1.
AK296482 mRNA. Translation: BAG59122.1.
AK304375 mRNA. Translation: BAG65213.1.
DQ667174 Genomic DNA. Translation: ABG25919.1.
AL359504, AL450063 Genomic DNA. Translation: CAI14540.1.
AL359504, AL450063 Genomic DNA. Translation: CAI14541.1.
AL450063, AL359504 Genomic DNA. Translation: CAI16844.1.
AL450063, AL359504 Genomic DNA. Translation: CAI16845.1.
AL450063 Genomic DNA. Translation: CAI16846.1.
CH471097 Genomic DNA. Translation: EAW73248.1.
BC016285 mRNA. Translation: AAH16285.1.
BC035058 mRNA. Translation: AAH35058.1.
AY927364 mRNA. Translation: AAX19487.1.
AY927365 mRNA. Translation: AAX19488.1.
AY927366 mRNA. Translation: AAX19489.1.
AY927367 mRNA. Translation: AAX19490.1.
AY927368 mRNA. Translation: AAX19491.1.
AF538872 Genomic DNA. Translation: AAN16454.1.
CCDSiCCDS55609.1. [P22694-9]
CCDS55610.1. [P22694-7]
CCDS55611.1. [P22694-10]
CCDS691.1. [P22694-1]
CCDS692.1. [P22694-8]
CCDS693.1. [P22694-2]
CCDS72813.1. [P22694-3]
CCDS72815.1. [P22694-6]
PIRiA34724. OKHUCB.
RefSeqiNP_001229786.1. NM_001242857.2. [P22694-9]
NP_001229787.1. NM_001242858.2. [P22694-3]
NP_001229788.1. NM_001242859.2. [P22694-7]
NP_001229789.1. NM_001242860.2. [P22694-6]
NP_001229790.1. NM_001242861.2. [P22694-10]
NP_001229791.1. NM_001242862.2.
NP_001287844.1. NM_001300915.1.
NP_001287845.1. NM_001300916.1.
NP_001287846.1. NM_001300917.1.
NP_002722.1. NM_002731.3. [P22694-1]
NP_891993.1. NM_182948.3. [P22694-2]
NP_997461.1. NM_207578.2. [P22694-8]
XP_005271076.1. XM_005271019.1. [P22694-4]
XP_006710821.1. XM_006710758.1. [P22694-5]
UniGeneiHs.487325.

Genome annotation databases

EnsembliENST00000370682; ENSP00000359716; ENSG00000142875. [P22694-7]
ENST00000370685; ENSP00000359719; ENSG00000142875. [P22694-2]
ENST00000370688; ENSP00000359722; ENSG00000142875. [P22694-8]
ENST00000370689; ENSP00000359723; ENSG00000142875. [P22694-1]
ENST00000394839; ENSP00000378315; ENSG00000142875. [P22694-10]
ENST00000446538; ENSP00000401252; ENSG00000142875. [P22694-9]
ENST00000610703; ENSP00000481980; ENSG00000142875. [P22694-3]
ENST00000614872; ENSP00000479722; ENSG00000142875. [P22694-6]
GeneIDi5567.
KEGGihsa:5567.
UCSCiuc001dji.4. human. [P22694-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKAPCB_HUMAN
AccessioniPrimary (citable) accession number: P22694
Secondary accession number(s): B1APG4
, B4DKB0, B4E2Q1, Q14VH1, Q59GC0, Q5BNE9, Q5BNF0, Q5BNF1, Q5BNF2, Q5BNF3, Q5CZ92, Q5T1K3, Q7Z3M1, Q8IYR5, Q8IZQ0, Q96B09
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: January 23, 2007
Last modified: September 27, 2017
This is version 190 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families