Seroatlas · Human Serome Atlas

PRKAR1A

cAMP-dependent protein kinase type I-alpha regulatory subunit

Also known as: CNC1, KAP0_HUMAN, PRKAR1, TSE1

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P10644
Gene: PRKAR1A
Ensembl: ENSG00000108946
Chromosome: 17
Canonical length: 381 aa
Protein class: Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins
Subcellular location: Cytosol

OverviewNCBI Gene

cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and 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. Four different regulatory subunits and three catalytic subunits have been identified in humans. This gene encodes one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids. Mutations in this gene cause Carney complex (CNC). This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2. A nonconventional nuclear localization sequence (NLS) has been found for this protein which suggests a role in DNA replication via the protein serving as a nuclear transport protein for the second subunit of the Replication Factor C (RFC40). Several alternatively spliced transcript variants encoding two different isoforms have been observed. [provided by RefSeq, Jan 2013]

Canonical amino-acid sequenceUniProt

381 residues, UniProt reviewed canonical sequence.

>P10644|PRKAR1A
     1  MESGSTAASE EARSLRECEL YVQKHNIQAL LKDSIVQLCT ARPERPMAFL REYFERLEKE
    61  EAKQIQNLQK AGTRTDSRED EISPPPPNPV VKGRRRRGAI SAEVYTEEDA ASYVRKVIPK
   121  DYKTMAALAK AIEKNVLFSH LDDNERSDIF DAMFSVSFIA GETVIQQGDE GDNFYVIDQG
   181  ETDVYVNNEW ATSVGEGGSF GELALIYGTP RAATVKAKTN VKLWGIDRDS YRRILMGSTL
   241  RKRKMYEEFL SKVSILESLD KWERLTVADA LEPVQFEDGQ KIVVQGEPGD EFFIILEGSA
   301  AVLQRRSENE EFVEVGRLGP SDYFGEIALL MNRPRAATVV ARGPLKCVKL DRPRFERVLG
   361  PCSDILKRNI QQYNSFVSLS V

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PRKAR1A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.34
Highest tissue expression: 378 nTPM

Expression across tissuesHPA

Tissue

heart muscle: 378 nTPM
parathyroid gland: 278 nTPM
skeletal muscle: 220 nTPM
ovary: 157 nTPM
thyroid gland: 157 nTPM
kidney: 149 nTPM

Single-cell type

late primary spermatocytes: 551 nCPM
neutrophils: 470 nCPM
early spermatids: 381 nCPM
respiratory ciliated cells: 367 nCPM
platelets: 310 nCPM
alveolar cells type 2: 292 nCPM

Immune cell

neutrophil: 232 nTPM
eosinophil: 204 nTPM
basophil: 162 nTPM
non-classical monocyte: 127 nTPM
total PBMC: 112 nTPM
classical monocyte: 109 nTPM

Brain region

pons: 264 nTPM
hypothalamus: 261 nTPM
midbrain: 243 nTPM
thalamus: 243 nTPM
medulla oblongata: 237 nTPM
white matter: 234 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PRKAR1A.

Disease | AllUniProt

Conditions PRKAR1A is implicated in, by any mechanism.

Carney complex 1 (CNC1) MIM:160980
Intracardiac myxoma (INTMYX) MIM:255960
Primary pigmented nodular adrenocortical disease 1 (PPNAD1) MIM:610489
Acrodysostosis 1, with or without hormone resistance (ACRDYS1) MIM:101800

Disease | GeneticClinVar

117 pathogenic / likely-pathogenic of 1,317 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Carney complex, type 1
Hereditary cancer-predisposing syndrome
Acrodysostosis 1 with or without hormone resistance
Familial atrial myxoma
Pigmented nodular adrenocortical disease, primary, 1

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.12
gnomAD pLI: 1
gnomAD missense Z: 3.12
DepMap mean gene effect: -0.18
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of PRKAR1A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads PRKAR1A as an antibody target. Whether an autoantibody or antibody against PRKAR1A could matter depends on whether native PRKAR1A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

PRKAR1A is annotated at the cell surface, where native PRKAR1A is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label PRKAR1A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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