Q9DBR0 · AKAP8_MOUSE

  • Protein
    A-kinase anchor protein 8
  • Gene
    Akap8
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Anchoring protein that mediates the subcellular compartmentation of cAMP-dependent protein kinase (PKA type II). Acts as an anchor for a PKA-signaling complex onto mitotic chromosomes, which is required for maintenance of chromosomes in a condensed form throughout mitosis. Recruits condensin complex subunit NCAPD2 to chromosomes required for chromatin condensation; the function appears to be independent from PKA-anchoring (By similarity).
Specifically involved in recruitment of CAPD2 to, and condensation of maternal but not paternal chromosomes (PubMed:12082153).
May help to deliver cyclin D/E to CDK4 to facilitate cell cycle progression (PubMed:14641107).
Required for cell cycle G2/M transition and histone deacetylation during mitosis. In mitotic cells recruits HDAC3 to the vicinity of chromatin leading to deacetylation and subsequent phosphorylation at 'Ser-10' of histone H3; in this function may act redundantly with AKAP8L. Involved in nuclear retention of RPS6KA1 upon ERK activation thus inducing cell proliferation. May be involved in regulation of DNA replication by acting as scaffold for MCM2. Enhances HMT activity of the KMT2 family MLL4/WBP7 complex and is involved in transcriptional regulation. In a teratocarcinoma cell line is involved in retinoic acid-mediated induction of developmental genes implicating H3 'Lys-4' methylation. May be involved in recruitment of active CASP3 to the nucleus in apoptotic cells. May act as a carrier protein of GJA1 for its transport to the nucleus. May play a repressive role in the regulation of rDNA transcription. Preferentially binds GC-rich DNA in vitro. In cells, associates with ribosomal RNA (rRNA) chromatin, preferentially with rRNA promoter and transcribed regions (By similarity).
Involved in modulation of Toll-like receptor signaling. Required for the cAMP-dependent suppression of TNF-alpha in early stages of LPS-induced macrophage activation; the function probably implicates targeting of PKA to NFKB1 (PubMed:19531803).

GO annotations

AspectTerm
Cellular Componentchromatin
Cellular Componentcondensed chromosome
Cellular Componentcytoplasm
Cellular Componentfemale pronucleus
Cellular Componentnuclear matrix
Cellular Componentnucleolus
Cellular Componentnucleoplasm
Cellular Componentnucleus
Molecular Functionchromatin binding
Molecular FunctionDNA binding
Molecular Functiondouble-stranded DNA binding
Molecular Functionhistone deacetylase binding
Molecular FunctionNF-kappaB binding
Molecular Functionprotein kinase A regulatory subunit binding
Molecular Functionzinc ion binding
Biological Processcell cycle G2/M phase transition
Biological Processcellular response to lipopolysaccharide
Biological Processcellular response to prostaglandin E stimulus
Biological Processinnate immune response
Biological Processmitotic chromosome condensation
Biological Processnegative regulation of tumor necrosis factor production
Biological Processprotein transport

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    A-kinase anchor protein 8
  • Short names
    AKAP-8
  • Alternative names
    • A-kinase anchor protein 95 kDa (AKAP 95)

Gene names

    • Name
      Akap8
    • Synonyms
      Akap95

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/6J
    • NOD
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9DBR0
  • Secondary accessions
    • Q9R0L8

Proteomes

Organism-specific databases

Subcellular Location

Nucleus matrix
Nucleus, nucleolus
Cytoplasm
Note: Associated with the nuclear matrix (By similarity).
Exhibits partial localization to the nucleolus in interphase, possibly to the fibrillary center and/or to the dense fibrillary component (By similarity).
Redistributed and detached from condensed chromatin during mitosis (By similarity).
Localizes specifically to the vicinity of the meiotic spindle in metaphase II oocytes (PubMed:12082153).

Keywords

Phenotypes & Variants

Disruption phenotype

AKAP8 and FIGN double mutant mice die soon after birth due to cleft palate.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 58 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, modified residue, cross-link.

TypeIDPosition(s)Description
ChainPRO_00000753821-687A-kinase anchor protein 8
Modified residue72Phosphoserine
Modified residue109Asymmetric dimethylarginine; alternate
Modified residue109Omega-N-methylarginine; alternate
Modified residue199Phosphoserine
Modified residue232Omega-N-methylarginine
Modified residue276Omega-N-methylarginine
Cross-link314Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Modified residue320Phosphoserine
Modified residue325Phosphoserine
Modified residue336Phosphoserine
Modified residue552Phosphothreonine
Modified residue659Phosphoserine

Post-translational modification

Phosphorylated on tyrosine residues probably by SRC subfamily protein kinases; multiple phosphorylation is leading to dissociation from nuclear structures implicated in chromatin structural changes.

Keywords

Proteomic databases

PTM databases

Expression

Developmental stage

Weakly expressed in metaphase II oocytes. Strongly up-regulated after fertilization at the pronuclear stage and restricted to the female pronucleus. Subsequently localized to the nucleus of each blastomere and on condensed chromosomes in mitotic cells.

Gene expression databases

Interaction

Subunit

Binds to the PKA RII-alpha regulatory subunit PRKAR2A (By similarity).
Interacts (via C-terminus) with FIGN (PubMed:16751186).
Interacts with NCAPD2, CCND3, CCNE1, MCM2, RPS6KA1, DDX5, PDE4A (By similarity).
Interacts with MYCBP; MYCBP is translocated to the nucleus and the interaction prevents the association of the PKA catalytic subunit leading to suppression of PKA activity (PubMed:12414807).
Interacts with CCND1, CASP3 (PubMed:14641107, PubMed:16227597).
Interacts with NFKB1; detetcted in the cytoplasm (PubMed:19531803).
Interacts with DPY30; mediating AKAP8 association with at least the MLL4/WBP7 HMT complex. Interacts with HDAC3; increased during mitosis. Interacts with GJA1; in the nucleus and in the nuclear membrane; the nuclear association increases with progress of cell cycle G1, S and G2 phase and decreases in M phase (By similarity).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q9DBR0Fign Q9ERZ64EBI-4285802, EBI-11111349
BINARY Q9DBR0Nfkb1 P257994EBI-4285802, EBI-643958

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, compositional bias, motif, zinc finger.

TypeIDPosition(s)Description
Region1-195Interaction with MCM2
Region1-210Interaction with DPY30
Region105-124Disordered
Region109-201Interaction with DDX5
Region185-218Disordered
Compositional bias194-218Polar residues
Region277-379Disordered
Compositional bias280-379Basic and acidic residues
Motif286-303Bipartite nuclear localization signal
Region384-447Involved in chromatin-binding
Zinc finger389-411C2H2 AKAP95-type 1
Zinc finger478-501C2H2 AKAP95-type 2
Region522-565Involved in condensin complex recruitment
Region568-585RII-binding
Region572-589Required for interaction with MYCBP
Compositional bias624-645Basic and acidic residues
Region624-659Disordered

Sequence similarities

Belongs to the AKAP95 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    687
  • Mass (Da)
    76,294
  • Last updated
    2001-06-01 v1
  • Checksum
    BC1E320216A47E10
MEQGYGGYGAWSAGPANTQGTYGSGMTSWQGYENYNYYNAQNTSVPAGTPYSYGPASWEATKTNDGGLAAGSPAMHVASFAPEPCTDNSDSLIAKINQRLDMLSKEGGRGGISSGGEGVQDRDSSFRFQPYESYDARPCIPEHNPYRPGYGYDYDFDLGTDRNGSFGGTFNDCRDPAPERGSLDGFLRGRGQGRFQDRSNSSTFIRSDPFMPPSASEPLSTTWNELNYMGGRGLGGPSTSRPPPSLFSQSMAPDYSMMGMQGVGGFGGTMPYGCGRSQTRIRDWPRRRGFERFGPDNMGRKRKQFPLYEEPDAKLARADSDGDLSENDDGAGDLRSGDEEFRGEDDLCDSRKQRGEKEDEDEDVKKRREKQRRRDRMRDRAADRIQFACSVCKFRSFEDEEIQKHLQSKFHKETLRFISTKLPDKTVEFLQEYIINRNKKIEKRRQELLEKESPKPKPDPFKGIGQEHFFKKIEAAHCLACDMLIPAQHQLLQRHLHSVDHNHNRRLAAEQFKKTSLHVAKSVLNNKHIVKMLEKYLKGEDPFVNETADLETEGDENVGEEKEETPEEVAAEVLAEVITAAVKAVEGEGEPAAAHSDVLTEVEGPVDTAEASSDPHTEKLLEEQTCEAASETRSIEDKTRGEAAEARNEAAMPTADAGSTLPVIAIPGIMEDELEQTGAEAKDIPTE

Computationally mapped potential isoform sequences

There are 7 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A494B9I1A0A494B9I1_MOUSEAkap8361
A0A494B966A0A494B966_MOUSEAkap860
A0A494B9L9A0A494B9L9_MOUSEAkap882
A0A494B9W0A0A494B9W0_MOUSEAkap855
A0A494BAT4A0A494BAT4_MOUSEAkap871
A0A494BAG5A0A494BAG5_MOUSEAkap859
A0A494BAZ0A0A494BAZ0_MOUSEAkap8148

Features

Showing features for compositional bias, sequence conflict.

TypeIDPosition(s)Description
Compositional bias194-218Polar residues
Compositional bias280-379Basic and acidic residues
Sequence conflict323in Ref. 1; BAA84710
Sequence conflict370in Ref. 1; BAA84710
Sequence conflict541in Ref. 1; BAA84710
Sequence conflict544in Ref. 1; BAA84710
Sequence conflict584in Ref. 1; BAA84710
Sequence conflict590in Ref. 1; BAA84710
Compositional bias624-645Basic and acidic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AB028920
EMBL· GenBank· DDBJ
BAA84710.1
EMBL· GenBank· DDBJ
mRNA
AK004801
EMBL· GenBank· DDBJ
BAB23574.1
EMBL· GenBank· DDBJ
mRNA
AK089092
EMBL· GenBank· DDBJ
BAC40746.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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