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Protein

cAMP-dependent protein kinase type II-alpha regulatory subunit

Gene

PRKAR2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei208cAMP 11
Binding sitei217cAMP 11
Binding sitei338cAMP 21
Binding sitei347cAMP 21

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi139 – 260cAMP 1Add BLAST122
Nucleotide bindingi261 – 404cAMP 2Add BLAST144

GO - Molecular functioni

  • cAMP binding Source: UniProtKB-KW
  • cAMP-dependent protein kinase inhibitor activity Source: BHF-UCL
  • cAMP-dependent protein kinase regulator activity Source: UniProtKB
  • protein kinase A catalytic subunit binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

cAMP, cAMP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000114302-MONOMER.
ReactomeiR-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-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-HSA-5610787. Hedgehog 'off' state.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SignaLinkiP13861.
SIGNORiP13861.

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-dependent protein kinase type II-alpha regulatory subunit
Gene namesi
Name:PRKAR2A
Synonyms:PKR2, PRKAR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:9391. PRKAR2A.

Subcellular locationi

GO - Cellular componenti

  • cAMP-dependent protein kinase complex Source: InterPro
  • centrosome Source: UniProtKB
  • ciliary base Source: Reactome
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • membrane Source: UniProtKB
  • nucleotide-activated protein kinase complex Source: BHF-UCL
  • plasma membrane Source: UniProtKB
  • plasma membrane raft Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi5576.
OpenTargetsiENSG00000114302.
PharmGKBiPA33757.

Polymorphism and mutation databases

BioMutaiPRKAR2A.
DMDMi125198.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002053852 – 404cAMP-dependent protein kinase type II-alpha regulatory subunitAdd BLAST403

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei48PhosphoserineCombined sources1
Modified residuei54PhosphothreonineCombined sources1
Modified residuei58PhosphoserineCombined sources1
Modified residuei78PhosphoserineCombined sources1
Modified residuei80PhosphoserineCombined sources1
Modified residuei99Phosphoserine; by PKACombined sources1
Modified residuei215Phosphothreonine; by PDPK1By similarity1
Modified residuei350PhosphoserineCombined sources1
Modified residuei395PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by the activated catalytic chain.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP13861.
MaxQBiP13861.
PaxDbiP13861.
PeptideAtlasiP13861.
PRIDEiP13861.

2D gel databases

OGPiP13861.

PTM databases

iPTMnetiP13861.
PhosphoSitePlusiP13861.

Expressioni

Tissue specificityi

Four types of regulatory chains are found: I-alpha, I-beta, II-alpha, and II-beta. Their expression varies among tissues and is in some cases constitutive and in others inducible.

Gene expression databases

BgeeiENSG00000114302.
CleanExiHS_PRKAR2A.
ExpressionAtlasiP13861. baseline and differential.
GenevisibleiP13861. HS.

Organism-specific databases

HPAiCAB005023.
HPA038268.

Interactioni

Subunit structurei

The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. Interacts with AKAP4 and CBFA2T3. Interacts with the phosphorylated form of PJA2. Interacts with MYRIP. This interaction may link PKA to components of the exocytosis machinery, thus facilitating exocytosis, including insulin release (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
P03259-25EBI-2556122,EBI-7225021From a different organism.
AKAP1Q926674EBI-2556122,EBI-2119593
AKAP3O759692EBI-2556122,EBI-9033101
AKAP5P245882EBI-2556122,EBI-703640
AKAP8O438233EBI-2556122,EBI-1237481

GO - Molecular functioni

  • protein kinase A catalytic subunit binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111562. 67 interactors.
DIPiDIP-552N.
IntActiP13861. 56 interactors.
MINTiMINT-5000495.
STRINGi9606.ENSP00000265563.

Structurei

Secondary structure

1404
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi10 – 24Combined sources15
Helixi29 – 43Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2IZXX-ray1.30A/B4-44[»]
2KYGNMR-A/B1-45[»]
4ZP3X-ray2.63A/B/C/D/E/F/G/H/I/J/K/L2-44[»]
ProteinModelPortaliP13861.
SMRiP13861.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13861.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 138Dimerization and phosphorylationAdd BLAST137

Sequence similaritiesi

Contains 2 cyclic nucleotide-binding domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1113. Eukaryota.
COG0664. LUCA.
GeneTreeiENSGT00530000062947.
HOGENOMiHOG000196668.
HOVERGENiHBG002025.
InParanoidiP13861.
KOiK04739.
OMAiMSERMKI.
OrthoDBiEOG091G0F1K.
PhylomeDBiP13861.
TreeFamiTF314920.

Family and domain databases

Gene3Di2.60.120.10. 2 hits.
InterProiIPR012198. cAMP_dep_PK_reg_su.
IPR003117. cAMP_dep_PK_reg_su_I/II_a/b.
IPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamiPF00027. cNMP_binding. 2 hits.
PF02197. RIIa. 1 hit.
[Graphical view]
PIRSFiPIRSF000548. PK_regulatory. 1 hit.
SMARTiSM00100. cNMP. 2 hits.
SM00394. RIIa. 1 hit.
[Graphical view]
SUPFAMiSSF47391. SSF47391. 1 hit.
SSF51206. SSF51206. 2 hits.
PROSITEiPS00888. CNMP_BINDING_1. 2 hits.
PS00889. CNMP_BINDING_2. 2 hits.
PS50042. CNMP_BINDING_3. 2 hits.
[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

Isoform 1 (identifier: P13861-1) [UniParc]FASTAAdd to basket

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
MSHIQIPPGL TELLQGYTVE VLRQQPPDLV EFAVEYFTRL REARAPASVL
60 70 80 90 100
PAATPRQSLG HPPPEPGPDR VADAKGDSES EEDEDLEVPV PSRFNRRVSV
110 120 130 140 150
CAETYNPDEE EEDTDPRVIH PKTDEQRCRL QEACKDILLF KNLDQEQLSQ
160 170 180 190 200
VLDAMFERIV KADEHVIDQG DDGDNFYVIE RGTYDILVTK DNQTRSVGQY
210 220 230 240 250
DNRGSFGELA LMYNTPRAAT IVATSEGSLW GLDRVTFRRI IVKNNAKKRK
260 270 280 290 300
MFESFIESVP LLKSLEVSER MKIVDVIGEK IYKDGERIIT QGEKADSFYI
310 320 330 340 350
IESGEVSILI RSRTKSNKDG GNQEVEIARC HKGQYFGELA LVTNKPRAAS
360 370 380 390 400
AYAVGDVKCL VMDVQAFERL LGPCMDIMKR NISHYEEQLV KMFGSSVDLG

NLGQ
Length:404
Mass (Da):45,518
Last modified:January 23, 2007 - v2
Checksum:iC7D6E8E476E1DB65
GO
Isoform 2 (identifier: P13861-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     292-313: Missing.

Show »
Length:382
Mass (Da):43,067
Checksum:i87D6AC1A5CE9E300
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056821292 – 313Missing in isoform 2. 2 PublicationsAdd BLAST22

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14968 mRNA. Translation: CAA33094.1.
BT007225 mRNA. Translation: AAP35889.1.
AC141002 Genomic DNA. No translation available.
AC144546 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64926.1.
CH471055 Genomic DNA. Translation: EAW64927.1.
BC002763 mRNA. Translation: AAH02763.1.
X99455 Genomic DNA. Translation: CAA67817.1.
CCDSiCCDS2778.1. [P13861-1]
CCDS82771.1. [P13861-2]
PIRiS03885. OKHU2R.
RefSeqiNP_001308911.1. NM_001321982.1. [P13861-1]
NP_001308912.1. NM_001321983.1. [P13861-2]
NP_004148.1. NM_004157.3. [P13861-1]
XP_011532244.1. XM_011533942.2. [P13861-1]
XP_016862304.1. XM_017006815.1. [P13861-1]
UniGeneiHs.631923.
Hs.731573.

Genome annotation databases

EnsembliENST00000265563; ENSP00000265563; ENSG00000114302. [P13861-1]
ENST00000296446; ENSP00000296446; ENSG00000114302. [P13861-2]
ENST00000454963; ENSP00000394041; ENSG00000114302. [P13861-1]
GeneIDi5576.
KEGGihsa:5576.
UCSCiuc003cux.2. human. [P13861-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X14968 mRNA. Translation: CAA33094.1.
BT007225 mRNA. Translation: AAP35889.1.
AC141002 Genomic DNA. No translation available.
AC144546 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64926.1.
CH471055 Genomic DNA. Translation: EAW64927.1.
BC002763 mRNA. Translation: AAH02763.1.
X99455 Genomic DNA. Translation: CAA67817.1.
CCDSiCCDS2778.1. [P13861-1]
CCDS82771.1. [P13861-2]
PIRiS03885. OKHU2R.
RefSeqiNP_001308911.1. NM_001321982.1. [P13861-1]
NP_001308912.1. NM_001321983.1. [P13861-2]
NP_004148.1. NM_004157.3. [P13861-1]
XP_011532244.1. XM_011533942.2. [P13861-1]
XP_016862304.1. XM_017006815.1. [P13861-1]
UniGeneiHs.631923.
Hs.731573.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2IZXX-ray1.30A/B4-44[»]
2KYGNMR-A/B1-45[»]
4ZP3X-ray2.63A/B/C/D/E/F/G/H/I/J/K/L2-44[»]
ProteinModelPortaliP13861.
SMRiP13861.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111562. 67 interactors.
DIPiDIP-552N.
IntActiP13861. 56 interactors.
MINTiMINT-5000495.
STRINGi9606.ENSP00000265563.

PTM databases

iPTMnetiP13861.
PhosphoSitePlusiP13861.

Polymorphism and mutation databases

BioMutaiPRKAR2A.
DMDMi125198.

2D gel databases

OGPiP13861.

Proteomic databases

EPDiP13861.
MaxQBiP13861.
PaxDbiP13861.
PeptideAtlasiP13861.
PRIDEiP13861.

Protocols and materials databases

DNASUi5576.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265563; ENSP00000265563; ENSG00000114302. [P13861-1]
ENST00000296446; ENSP00000296446; ENSG00000114302. [P13861-2]
ENST00000454963; ENSP00000394041; ENSG00000114302. [P13861-1]
GeneIDi5576.
KEGGihsa:5576.
UCSCiuc003cux.2. human. [P13861-1]

Organism-specific databases

CTDi5576.
DisGeNETi5576.
GeneCardsiPRKAR2A.
HGNCiHGNC:9391. PRKAR2A.
HPAiCAB005023.
HPA038268.
MIMi176910. gene.
neXtProtiNX_P13861.
OpenTargetsiENSG00000114302.
PharmGKBiPA33757.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1113. Eukaryota.
COG0664. LUCA.
GeneTreeiENSGT00530000062947.
HOGENOMiHOG000196668.
HOVERGENiHBG002025.
InParanoidiP13861.
KOiK04739.
OMAiMSERMKI.
OrthoDBiEOG091G0F1K.
PhylomeDBiP13861.
TreeFamiTF314920.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000114302-MONOMER.
ReactomeiR-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-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-HSA-5610787. Hedgehog 'off' state.
R-HSA-983231. Factors involved in megakaryocyte development and platelet production.
SignaLinkiP13861.
SIGNORiP13861.

Miscellaneous databases

ChiTaRSiPRKAR2A. human.
EvolutionaryTraceiP13861.
GeneWikiiPRKAR2A.
GenomeRNAii5576.
PROiP13861.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114302.
CleanExiHS_PRKAR2A.
ExpressionAtlasiP13861. baseline and differential.
GenevisibleiP13861. HS.

Family and domain databases

Gene3Di2.60.120.10. 2 hits.
InterProiIPR012198. cAMP_dep_PK_reg_su.
IPR003117. cAMP_dep_PK_reg_su_I/II_a/b.
IPR018490. cNMP-bd-like.
IPR018488. cNMP-bd_CS.
IPR000595. cNMP-bd_dom.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamiPF00027. cNMP_binding. 2 hits.
PF02197. RIIa. 1 hit.
[Graphical view]
PIRSFiPIRSF000548. PK_regulatory. 1 hit.
SMARTiSM00100. cNMP. 2 hits.
SM00394. RIIa. 1 hit.
[Graphical view]
SUPFAMiSSF47391. SSF47391. 1 hit.
SSF51206. SSF51206. 2 hits.
PROSITEiPS00888. CNMP_BINDING_1. 2 hits.
PS00889. CNMP_BINDING_2. 2 hits.
PS50042. CNMP_BINDING_3. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKAP2_HUMAN
AccessioniPrimary (citable) accession number: P13861
Secondary accession number(s): Q16823, Q9BUB1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 177 of the entry and version 2 of the sequence. [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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.