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P13861 (KAP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
cAMP-dependent protein kinase type II-alpha regulatory subunit
Gene names
Name:PRKAR2A
Synonyms:PKR2, PRKAR2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length404 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Ref.3 Ref.7 Ref.17

Subcellular location

Cytoplasm. Cell membrane. Note: Colocalizes with PJA2 in the cytoplasm and the cell membrane. Ref.17

Tissue specificity

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.

Post-translational modification

Phosphorylated by the activated catalytic chain.

Sequence similarities

Belongs to the cAMP-dependent kinase regulatory chain family.

Contains 2 cyclic nucleotide-binding domains.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
   DomainRepeat
   LigandcAMP
cAMP-binding
Nucleotide-binding
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of phospholipase C activity

Traceable author statement. Source: Reactome

activation of protein kinase A activity

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

cellular response to glucagon stimulus

Traceable author statement. Source: Reactome

energy reserve metabolic process

Traceable author statement. Source: Reactome

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

intracellular signal transduction

Traceable author statement Ref.1. Source: ProtInc

negative regulation of cAMP-dependent protein kinase activity

Inferred from direct assay PubMed 21812984. Source: BHF-UCL

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

regulation of insulin secretion

Traceable author statement. Source: Reactome

signal transduction

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

water transport

Traceable author statement. Source: Reactome

   Cellular_componentAMP-activated protein kinase complex

Inferred from direct assay PubMed 21812984. Source: BHF-UCL

cAMP-dependent protein kinase complex

Inferred from electronic annotation. Source: InterPro

centrosome

Inferred from direct assay PubMed 21399614. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.17. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 20458337. Source: UniProt

membrane

Traceable author statement PubMed 10799517. Source: ProtInc

plasma membrane

Inferred from direct assay Ref.17. Source: UniProtKB

   Molecular_functioncAMP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cAMP-dependent protein kinase inhibitor activity

Inferred from direct assay PubMed 21812984. Source: BHF-UCL

cAMP-dependent protein kinase regulator activity

Non-traceable author statement Ref.2. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 11278869PubMed 11414803PubMed 16642035PubMed 24083380. Source: IntAct

protein kinase A catalytic subunit binding

Inferred from physical interaction PubMed 21812984. Source: BHF-UCL

ubiquitin protein ligase binding

Inferred from direct assay Ref.17. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

P03259-25EBI-2556122,EBI-7225021From a different organism.
AKAP1Q926673EBI-2556122,EBI-2119593
AKAP3O759692EBI-2556122,EBI-9033101

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.19
Chain2 – 404403cAMP-dependent protein kinase type II-alpha regulatory subunit
PRO_0000205385

Regions

Nucleotide binding139 – 260122cAMP 1
Nucleotide binding261 – 404144cAMP 2
Region2 – 138137Dimerization and phosphorylation

Sites

Binding site2081cAMP 1
Binding site2171cAMP 1
Binding site3381cAMP 2
Binding site3471cAMP 2

Amino acid modifications

Modified residue21N-acetylserine Ref.19
Modified residue481Phosphoserine Ref.15
Modified residue541Phosphothreonine Ref.10 Ref.15
Modified residue581Phosphoserine Ref.10 Ref.15
Modified residue781Phosphoserine Ref.10 Ref.14 Ref.15 Ref.18
Modified residue801Phosphoserine Ref.10 Ref.14 Ref.15 Ref.18
Modified residue991Phosphoserine; by PKA Ref.4 Ref.10 Ref.11 Ref.14
Modified residue2151Phosphothreonine; by PDPK1 By similarity

Secondary structure

..... 404
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P13861 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: C7D6E8E476E1DB65

FASTA40445,518
        10         20         30         40         50         60 
MSHIQIPPGL TELLQGYTVE VLRQQPPDLV EFAVEYFTRL REARAPASVL PAATPRQSLG 

        70         80         90        100        110        120 
HPPPEPGPDR VADAKGDSES EEDEDLEVPV PSRFNRRVSV CAETYNPDEE EEDTDPRVIH 

       130        140        150        160        170        180 
PKTDEQRCRL QEACKDILLF KNLDQEQLSQ VLDAMFERIV KADEHVIDQG DDGDNFYVIE 

       190        200        210        220        230        240 
RGTYDILVTK DNQTRSVGQY DNRGSFGELA LMYNTPRAAT IVATSEGSLW GLDRVTFRRI 

       250        260        270        280        290        300 
IVKNNAKKRK MFESFIESVP LLKSLEVSER MKIVDVIGEK IYKDGERIIT QGEKADSFYI 

       310        320        330        340        350        360 
IESGEVSILI RSRTKSNKDG GNQEVEIARC HKGQYFGELA LVTNKPRAAS AYAVGDVKCL 

       370        380        390        400 
VMDVQAFERL LGPCMDIMKR NISHYEEQLV KMFGSSVDLG NLGQ 

« Hide

References

« Hide 'large scale' references
[1]"Human testis cDNA for the regulatory subunit RII alpha of cAMP-dependent protein kinase encodes an alternate amino-terminal region."
Oyen O., Myklebust F., Scott J.D., Hansson V., Jahnsen T.
FEBS Lett. 246:57-64(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Testis.
[2]"Molecular cloning, upstream sequence and promoter studies of the human gene for the regulatory subunit RII alpha of cAMP-dependent protein kinase."
Foss K.B., Solberg R., Simard J., Myklebust F., Hansson V., Jahnsen T., Tasken K.
Biochim. Biophys. Acta 1350:98-108(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-87.
[3]"Identification and characterization of myeloid translocation gene 16b as a novel a kinase anchoring protein in T lymphocytes."
Schillace R.V., Andrews S.F., Liberty G.A., Davey M.P., Carr D.W.
J. Immunol. 168:1590-1599(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CBFA2T3.
[4]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[5]"Phosphoproteomic analysis of the human pituitary."
Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.
Pituitary 9:109-120(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Pituitary.
[6]"Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line."
Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.
Electrophoresis 28:2027-2034(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Prostate cancer.
[7]"MyRIP anchors protein kinase A to the exocyst complex."
Goehring A.S., Pedroja B.S., Hinke S.A., Langeberg L.K., Scott J.D.
J. Biol. Chem. 282:33155-33167(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MYRIP.
[8]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[9]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-54; SER-58; SER-78; SER-80 AND SER-99, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography."
Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J.
Proteomics 8:1346-1361(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[12]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78; SER-80 AND SER-99, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[15]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48; THR-54; SER-58; SER-78 AND SER-80, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[16]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Control of PKA stability and signalling by the RING ligase praja2."
Lignitto L., Carlucci A., Sepe M., Stefan E., Cuomo O., Nistico R., Scorziello A., Savoia C., Garbi C., Annunziato L., Feliciello A.
Nat. Cell Biol. 13:412-422(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PJA2.
[18]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-78 AND SER-80, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X14968 mRNA. Translation: CAA33094.1.
X99455 Genomic DNA. Translation: CAA67817.1.
CCDSCCDS2778.1.
PIROKHU2R. S03885.
RefSeqNP_004148.1. NM_004157.2.
XP_005265370.1. XM_005265313.1.
UniGeneHs.631923.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2IZXX-ray1.30A/B4-44[»]
2KYGNMR-A/B1-45[»]
ProteinModelPortalP13861.
SMRP13861. Positions 4-396.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111562. 39 interactions.
DIPDIP-552N.
IntActP13861. 19 interactions.
MINTMINT-5000495.
STRING9606.ENSP00000265563.

Chemistry

BindingDBP13861.

PTM databases

PhosphoSiteP13861.

Polymorphism databases

DMDM125198.

2D gel databases

OGPP13861.

Proteomic databases

MaxQBP13861.
PaxDbP13861.
PRIDEP13861.

Protocols and materials databases

DNASU5576.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265563; ENSP00000265563; ENSG00000114302.
ENST00000454963; ENSP00000394041; ENSG00000114302.
GeneID5576.
KEGGhsa:5576.
UCSCuc003cux.1. human.

Organism-specific databases

CTD5576.
GeneCardsGC03M048762.
HGNCHGNC:9391. PRKAR2A.
HPACAB005023.
MIM176910. gene.
neXtProtNX_P13861.
PharmGKBPA33757.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0664.
HOGENOMHOG000196668.
HOVERGENHBG002025.
InParanoidP13861.
KOK04739.
OMALEMSERM.
PhylomeDBP13861.
TreeFamTF314920.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_116125. Disease.
REACT_15518. Transmembrane transport of small molecules.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkP13861.

Gene expression databases

ArrayExpressP13861.
BgeeP13861.
CleanExHS_PRKAR2A.
GenevestigatorP13861.

Family and domain databases

Gene3D2.60.120.10. 2 hits.
InterProIPR002373. cAMP/cGMP_kin.
IPR012198. 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]
PfamPF00027. cNMP_binding. 2 hits.
PF02197. RIIa. 1 hit.
[Graphical view]
PIRSFPIRSF000548. PK_regulatory. 1 hit.
PRINTSPR00103. CAMPKINASE.
SMARTSM00100. cNMP. 2 hits.
SM00394. RIIa. 1 hit.
[Graphical view]
SUPFAMSSF47391. SSF47391. 1 hit.
SSF51206. SSF51206. 2 hits.
PROSITEPS00888. CNMP_BINDING_1. 2 hits.
PS00889. CNMP_BINDING_2. 2 hits.
PS50042. CNMP_BINDING_3. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPRKAR2A. human.
EvolutionaryTraceP13861.
GeneWikiPRKAR2A.
GenomeRNAi5576.
NextBio21620.
PROP13861.
SOURCESearch...

Entry information

Entry nameKAP2_HUMAN
AccessionPrimary (citable) accession number: P13861
Secondary accession number(s): Q16823
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM