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UniProtKB - P10644 (KAP0_HUMAN)

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Protein

cAMP-dependent protein kinase type I-alpha regulatory subunit

Gene

PRKAR1A

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

Functioni

Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei202cAMP 11
Binding sitei211cAMP 11
Binding sitei326cAMP 21
Binding sitei335cAMP 21

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi137 – 254cAMP 1Add BLAST118
Nucleotide bindingi255 – 381cAMP 2Add BLAST127

GO - Molecular functioni

  • cAMP binding Source: UniProtKB-KW
  • cAMP-dependent protein kinase inhibitor activity Source: BHF-UCL
  • cAMP-dependent protein kinase regulator activity Source: BHF-UCL
  • protein domain specific binding Source: UniProtKB
  • protein kinase A catalytic subunit binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

LigandcAMP, cAMP-binding, Nucleotide-binding

Enzyme and pathway databases

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
SignaLinkiP10644
SIGNORiP10644

Names & Taxonomyi

Protein namesi
Recommended name:
cAMP-dependent protein kinase type I-alpha regulatory subunit
Alternative name(s):
Tissue-specific extinguisher 1
Short name:
TSE1
Gene namesi
Name:PRKAR1A
Synonyms:PKR1, PRKAR1, TSE1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000108946.14
HGNCiHGNC:9388 PRKAR1A
MIMi188830 gene
neXtProtiNX_P10644

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, Membrane

Pathology & Biotechi

Involvement in diseasei

Carney complex 1 (CNC1)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCNC is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumors, and psammomatous melanotic schwannomas.
See also OMIM:160980
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0468949S → N in CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit. 1 Publication1
Natural variantiVAR_04689574R → C in CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit. 2 PublicationsCorresponds to variant dbSNP:rs137853303EnsemblClinVar.1
Natural variantiVAR_046896146R → S in CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit. 1 Publication1
Natural variantiVAR_046897183D → Y in CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit. 1 Publication1
Natural variantiVAR_046898213A → D in CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit; reduces protein degradation. 2 PublicationsCorresponds to variant dbSNP:rs281864786EnsemblClinVar.1
Natural variantiVAR_046899289G → W in CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit; accelerates protein degradation. 2 Publications1
Intracardiac myxoma (INTMYX)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionInheritance is autosomal recessive.
See also OMIM:255960
Primary pigmented nodular adrenocortical disease 1 (PPNAD1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. PPNAD1 is most often diagnosed in patients with Carney complex, a multiple neoplasia syndrome. However it can also be observed in patients without other manifestations.
See also OMIM:610489
Acrodysostosis 1, with or without hormone resistance (ACRDYS1)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of skeletal dysplasia characterized by short stature, severe brachydactyly, facial dysostosis, and nasal hypoplasia. Affected individuals often have advanced bone age and obesity. Laboratory studies show resistance to multiple hormones, including parathyroid, thyrotropin, calcitonin, growth hormone-releasing hormone, and gonadotropin. However, not all patients show endocrine abnormalities.
See also OMIM:101800
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075533175Y → C in ACRDYS1; reduces PKA activity; decreases cAMP binding. 1 Publication1
Natural variantiVAR_069456213A → T in ACRDYS1; reduces PKA activity; decreases cAMP binding; reduces protein degradation. 2 Publications1
Natural variantiVAR_069458239T → A in ACRDYS1; impairs response of PKA to c-AMP. 1 Publication1
Natural variantiVAR_069459285Q → R in ACRDYS1; reduces PKA activity; decreases cAMP binding. 2 Publications1
Natural variantiVAR_069460289G → E in ACRDYS1; reduces PKA activity; decreases cAMP binding; reduces protein degradation. 2 Publications1
Natural variantiVAR_069461327I → T in ACRDYS1. 1 PublicationCorresponds to variant dbSNP:rs387906695EnsemblClinVar.1
Natural variantiVAR_069462328A → V in ACRDYS1; disrupts cAMP binding. 2 Publications1
Natural variantiVAR_069464335R → L in ACRDYS1; disrupts cAMP binding. 2 Publications1
Natural variantiVAR_069463335R → P in ACRDYS1. 1 PublicationCorresponds to variant dbSNP:rs387906694EnsemblClinVar.1
Natural variantiVAR_069465373Y → C in ACRDYS1. 1 Publication1
Natural variantiVAR_068241373Y → H in ACRDYS1. 1 PublicationCorresponds to variant dbSNP:rs387906693EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi373Y → A: Impairs response of PKA to c-AMP. 1 Publication1

Keywords - Diseasei

Cushing syndrome, Disease mutation

Organism-specific databases

DisGeNETi5573
GeneReviewsiPRKAR1A
MalaCardsiPRKAR1A
MIMi101800 phenotype
160980 phenotype
255960 phenotype
610489 phenotype
OpenTargetsiENSG00000108946
Orphaneti950 Acrodysostosis
280651 Acrodysostosis with multiple hormone resistance
520 Acute promyelocytic leukemia
1359 Carney complex
615 Familial atrial myxoma
189439 Primary pigmented nodular adrenocortical disease
PharmGKBiPA33754

Chemistry databases

DrugBankiDB02527 Cyclic Adenosine Monophosphate
DB02315 Cyclic Guanosine Monophosphate
DB05798 GEM-231
GuidetoPHARMACOLOGYi1472

Polymorphism and mutation databases

DMDMi125193

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002053771 – 381cAMP-dependent protein kinase type I-alpha regulatory subunitAdd BLAST381

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1 Publication1
Modified residuei3PhosphoserineBy similarity1
Disulfide bondi18Interchain (with C-39)By similarity
Disulfide bondi39Interchain (with C-18)By similarity
Modified residuei75PhosphothreonineCombined sources1
Modified residuei77PhosphoserineCombined sources1
Modified residuei83PhosphoserineCombined sources1
Modified residuei101PhosphoserineBy similarity1
Modified residuei258PhosphoserineBy similarity1

Post-translational modificationi

The pseudophosphorylation site binds to the substrate-binding region of the catalytic chain, resulting in the inhibition of its activity.

Keywords - PTMi

Acetylation, Disulfide bond, Phosphoprotein

Proteomic databases

EPDiP10644
MaxQBiP10644
PaxDbiP10644
PeptideAtlasiP10644
PRIDEiP10644
ProteomicsDBi52634

2D gel databases

OGPiP10644
REPRODUCTION-2DPAGEiIPI00021831

PTM databases

iPTMnetiP10644
PhosphoSitePlusiP10644
SwissPalmiP10644

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

BgeeiENSG00000108946
CleanExiHS_PRKAR1A
ExpressionAtlasiP10644 baseline and differential
GenevisibleiP10644 HS

Organism-specific databases

HPAiCAB019378
HPA049979

Interactioni

Subunit structurei

The inactive holoenzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP releases the two active catalytic monomers and the regulatory dimer. PRKAR1A also interacts with RFC2; the complex may be involved in cell survival. Interacts with AKAP4. Interacts with RARA; the interaction occurs in the presence of cAMP or FSH and regulates RARA transcriptional activity. Interacts with the phosphorylated form of PJA2. Interacts with CBFA2T3 (By similarity). Interacts with PRKX; regulates this cAMP-dependent protein kinase. Interacts with C2orf88/smAKAP; this interaction may target PRKAR1A to the plasma membrane. Interacts with AICDA.By similarity6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB
  • protein kinase A catalytic subunit binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi111559, 91 interactors
DIPiDIP-34368N
IntActiP10644, 87 interactors
MINTiP10644
STRINGi9606.ENSP00000351410

Chemistry databases

BindingDBiP10644

Structurei

Secondary structure

1381
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi237 – 250Combined sources14
Helixi254 – 256Combined sources3
Helixi261 – 270Combined sources10
Beta strandi272 – 276Combined sources5
Beta strandi281 – 283Combined sources3
Beta strandi291 – 304Combined sources14
Beta strandi313 – 318Combined sources6
Helixi326 – 330Combined sources5
Beta strandi336 – 351Combined sources16
Helixi352 – 358Combined sources7
Helixi360 – 362Combined sources3
Helixi363 – 370Combined sources8
Turni371 – 376Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5KJXX-ray1.90A234-381[»]
5KJYX-ray2.00A234-381[»]
5KJZX-ray1.35A234-381[»]
ProteinModelPortaliP10644
SMRiP10644
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 136Dimerization and phosphorylationAdd BLAST136

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi96 – 100Pseudophosphorylation motif5

Sequence similaritiesi

Belongs to the cAMP-dependent kinase regulatory chain family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1113 Eukaryota
COG0664 LUCA
GeneTreeiENSGT00530000062947
HOGENOMiHOG000196669
HOVERGENiHBG002025
InParanoidiP10644
KOiK04739
OMAiVQLCTVR
OrthoDBiEOG091G0F1K
PhylomeDBiP10644
TreeFamiTF314920

Family and domain databases

CDDicd00038 CAP_ED, 2 hits
Gene3Di2.60.120.10, 2 hits
InterProiView protein in InterPro
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
PfamiView protein in Pfam
PF00027 cNMP_binding, 2 hits
PF02197 RIIa, 1 hit
PIRSFiPIRSF000548 PK_regulatory, 1 hit
SMARTiView protein in SMART
SM00100 cNMP, 2 hits
SM00394 RIIa, 1 hit
SUPFAMiSSF51206 SSF51206, 2 hits
PROSITEiView protein in PROSITE
PS00888 CNMP_BINDING_1, 2 hits
PS00889 CNMP_BINDING_2, 2 hits
PS50042 CNMP_BINDING_3, 2 hits

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: P10644-1) [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
MESGSTAASE EARSLRECEL YVQKHNIQAL LKDSIVQLCT ARPERPMAFL 
        60         70         80         90        100
REYFERLEKE EAKQIQNLQK AGTRTDSRED EISPPPPNPV VKGRRRRGAI 
       110        120        130        140        150
SAEVYTEEDA ASYVRKVIPK DYKTMAALAK AIEKNVLFSH LDDNERSDIF 
       160        170        180        190        200
DAMFSVSFIA GETVIQQGDE GDNFYVIDQG ETDVYVNNEW ATSVGEGGSF 
       210        220        230        240        250
GELALIYGTP RAATVKAKTN VKLWGIDRDS YRRILMGSTL RKRKMYEEFL 
       260        270        280        290        300
SKVSILESLD KWERLTVADA LEPVQFEDGQ KIVVQGEPGD EFFIILEGSA 
       310        320        330        340        350
AVLQRRSENE EFVEVGRLGP SDYFGEIALL MNRPRAATVV ARGPLKCVKL 
       360        370        380 
DRPRFERVLG PCSDILKRNI QQYNSFVSLS V
Length:381
Mass (Da):42,982
Last modified:July 1, 1989 - v1
Checksum:i2D04F08CE8857A6D
GO
Isoform 2 (identifier: P10644-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     326-337: EIALLMNRPRAA → HLIISRRSIPLG
     338-381: Missing.

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:337
Mass (Da):38,003
Checksum:i8C14AF540F3150CF
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0468949S → N in CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit. 1 Publication1
Natural variantiVAR_04689574R → C in CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit. 2 PublicationsCorresponds to variant dbSNP:rs137853303EnsemblClinVar.1
Natural variantiVAR_046896146R → S in CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit. 1 Publication1
Natural variantiVAR_075533175Y → C in ACRDYS1; reduces PKA activity; decreases cAMP binding. 1 Publication1
Natural variantiVAR_046897183D → Y in CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit. 1 Publication1
Natural variantiVAR_046898213A → D in CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit; reduces protein degradation. 2 PublicationsCorresponds to variant dbSNP:rs281864786EnsemblClinVar.1
Natural variantiVAR_069456213A → T in ACRDYS1; reduces PKA activity; decreases cAMP binding; reduces protein degradation. 2 Publications1
Natural variantiVAR_069457227D → N1 Publication1
Natural variantiVAR_069458239T → A in ACRDYS1; impairs response of PKA to c-AMP. 1 Publication1
Natural variantiVAR_069459285Q → R in ACRDYS1; reduces PKA activity; decreases cAMP binding. 2 Publications1
Natural variantiVAR_069460289G → E in ACRDYS1; reduces PKA activity; decreases cAMP binding; reduces protein degradation. 2 Publications1
Natural variantiVAR_046899289G → W in CNC1; exhibits increased PKA activity which is attributed to decreased binding to cAMP and/or the catalytic subunit; accelerates protein degradation. 2 Publications1
Natural variantiVAR_069461327I → T in ACRDYS1. 1 PublicationCorresponds to variant dbSNP:rs387906695EnsemblClinVar.1
Natural variantiVAR_069462328A → V in ACRDYS1; disrupts cAMP binding. 2 Publications1
Natural variantiVAR_069464335R → L in ACRDYS1; disrupts cAMP binding. 2 Publications1
Natural variantiVAR_069463335R → P in ACRDYS1. 1 PublicationCorresponds to variant dbSNP:rs387906694EnsemblClinVar.1
Natural variantiVAR_069465373Y → C in ACRDYS1. 1 Publication1
Natural variantiVAR_068241373Y → H in ACRDYS1. 1 PublicationCorresponds to variant dbSNP:rs387906693EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054833326 – 337EIALL…RPRAA → HLIISRRSIPLG in isoform 2. CuratedAdd BLAST12
Alternative sequenceiVSP_054834338 – 381Missing in isoform 2. CuratedAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M18468 mRNA Translation: AAB50922.1
M33336 mRNA Translation: AAB50921.1
S54705 mRNA No translation available.
S54707 mRNA No translation available.
S54709 mRNA No translation available.
S54711 mRNA No translation available.
Y07642 mRNA Translation: CAA68925.1
AC079210 Genomic DNA No translation available.
BC036285 mRNA Translation: AAH36285.1
BC093042 mRNA Translation: AAH93042.1
CCDSiCCDS11678.1 [P10644-1]
CCDS62307.1 [P10644-2]
PIRiA34627 OKHU1R
RefSeqiNP_001263218.1, NM_001276289.1 [P10644-1]
NP_001263219.1, NM_001276290.1 [P10644-2]
NP_001265362.1, NM_001278433.1 [P10644-1]
NP_002725.1, NM_002734.4 [P10644-1]
NP_997636.1, NM_212471.2 [P10644-1]
NP_997637.1, NM_212472.2 [P10644-1]
XP_011523285.1, XM_011524983.2 [P10644-1]
XP_011523286.1, XM_011524984.2 [P10644-1]
XP_011523287.1, XM_011524985.2 [P10644-1]
UniGeneiHs.280342
Hs.745160

Genome annotation databases

EnsembliENST00000358598; ENSP00000351410; ENSG00000108946 [P10644-1]
ENST00000392711; ENSP00000376475; ENSG00000108946 [P10644-1]
ENST00000536854; ENSP00000445625; ENSG00000108946 [P10644-1]
ENST00000586397; ENSP00000466459; ENSG00000108946 [P10644-1]
ENST00000588188; ENSP00000468106; ENSG00000108946 [P10644-2]
ENST00000589228; ENSP00000464977; ENSG00000108946 [P10644-1]
GeneIDi5573
KEGGihsa:5573
UCSCiuc002jhg.5 human [P10644-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKAP0_HUMAN
AccessioniPrimary (citable) accession number: P10644
Secondary accession number(s): K7ER48, Q567S7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: June 20, 2018
This is version 213 of the entry and version 1 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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