This gene encodes one of the catalytic subunits of protein kinase A, which exists as a tetrameric holoenzyme with two regulatory subunits and two catalytic subunits, in its inactive form. 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. cAMP-dependent phosphorylation of proteins by protein kinase A is important to many cellular processes, including differentiation, proliferation, and apoptosis. Constitutive activation of this gene caused either by somatic mutations, or genomic duplications of regions that include this gene, have been associated with hyperplasias and adenomas of the adrenal cortex and are linked to corticotropin-independent Cushing's syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. Tissue-specific isoforms that differ at the N-terminus have been described, and these isoforms may differ in the post-translational modifications that occur at the N-terminus of some isoforms. [provided by RefSeq, Jan 2015].
Description
This track shows human genome high-confidence gene annotations from the
Consensus
Coding Sequence (CCDS) project. This project is a collaborative effort
to identify a core set of
human protein-coding regions that are consistently annotated and of high
quality. The long-term goal is to support convergence towards a standard set
of gene annotations on the human genome.
Collaborators include:
For more information on the different gene tracks, see our Genes FAQ.
Methods
CDS annotations of the human genome were obtained from two sources:
NCBI
RefSeq and a union of the gene annotations from
Ensembl and
Vega, collectively known
as Hinxton.
Genes with identical CDS genomic coordinates in both sets become CCDS
candidates. The genes undergo a quality evaluation, which must be approved by
all collaborators. The following criteria are currently used to assess each
gene:
- an initiating ATG (Exception: a non-ATG translation start codon is
annotated if it has sufficient experimental support), a valid stop codon, and
no in-frame stop codons (Exception: selenoproteins, which contain a TGA codon
that is known to be translated to a selenocysteine instead of functioning as
a stop codon)
- ability to be translated from the genome reference sequence without frameshifts
- recognizable splicing sites
- no intersection with putative pseudogene predictions
- supporting transcripts and protein homology
- conservation evidence with other species
A unique CCDS ID is assigned to the CCDS, which links together all gene
annotations with the same CDS. CCDS gene annotations are under continuous
review, with periodic updates to this track.
Credits
This track was produced at UCSC from data downloaded from the
CCDS project
web site.
References
Hubbard T, Barker D, Birney E, Cameron G, Chen Y, Clark L, Cox T, Cuff J, Curwen V, Down T et
al.
The Ensembl genome database project.
Nucleic Acids Res. 2002 Jan 1;30(1):38-41.
PMID: 11752248; PMC: PMC99161
Pruitt KD, Harrow J, Harte RA, Wallin C, Diekhans M, Maglott DR, Searle S, Farrell CM, Loveland JE,
Ruef BJ et al.
The consensus coding sequence (CCDS) project: Identifying a common protein-coding gene set for the
human and mouse genomes.
Genome Res. 2009 Jul;19(7):1316-23.
PMID: 19498102; PMC: PMC2704439
Pruitt KD, Tatusova T, Maglott DR.
NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts
and proteins.
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D501-4.
PMID: 15608248; PMC: PMC539979
US Server