Q9DBR0 · AKAP8_MOUSE
- ProteinA-kinase anchor protein 8
- GeneAkap8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids687 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
Aspect | Term | |
---|---|---|
Cellular Component | chromatin | |
Cellular Component | condensed chromosome | |
Cellular Component | cytoplasm | |
Cellular Component | female pronucleus | |
Cellular Component | nuclear matrix | |
Cellular Component | nucleolus | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | chromatin binding | |
Molecular Function | DNA binding | |
Molecular Function | double-stranded DNA binding | |
Molecular Function | histone deacetylase binding | |
Molecular Function | NF-kappaB binding | |
Molecular Function | protein kinase A regulatory subunit binding | |
Molecular Function | zinc ion binding | |
Biological Process | cell cycle G2/M phase transition | |
Biological Process | cellular response to lipopolysaccharide | |
Biological Process | cellular response to prostaglandin E stimulus | |
Biological Process | innate immune response | |
Biological Process | mitotic chromosome condensation | |
Biological Process | negative regulation of tumor necrosis factor production | |
Biological Process | protein transport |
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameA-kinase anchor protein 8
- Short namesAKAP-8
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9DBR0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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).
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
- Cellular component
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.
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000075382 | 1-687 | A-kinase anchor protein 8 | |||
Sequence: MEQGYGGYGAWSAGPANTQGTYGSGMTSWQGYENYNYYNAQNTSVPAGTPYSYGPASWEATKTNDGGLAAGSPAMHVASFAPEPCTDNSDSLIAKINQRLDMLSKEGGRGGISSGGEGVQDRDSSFRFQPYESYDARPCIPEHNPYRPGYGYDYDFDLGTDRNGSFGGTFNDCRDPAPERGSLDGFLRGRGQGRFQDRSNSSTFIRSDPFMPPSASEPLSTTWNELNYMGGRGLGGPSTSRPPPSLFSQSMAPDYSMMGMQGVGGFGGTMPYGCGRSQTRIRDWPRRRGFERFGPDNMGRKRKQFPLYEEPDAKLARADSDGDLSENDDGAGDLRSGDEEFRGEDDLCDSRKQRGEKEDEDEDVKKRREKQRRRDRMRDRAADRIQFACSVCKFRSFEDEEIQKHLQSKFHKETLRFISTKLPDKTVEFLQEYIINRNKKIEKRRQELLEKESPKPKPDPFKGIGQEHFFKKIEAAHCLACDMLIPAQHQLLQRHLHSVDHNHNRRLAAEQFKKTSLHVAKSVLNNKHIVKMLEKYLKGEDPFVNETADLETEGDENVGEEKEETPEEVAAEVLAEVITAAVKAVEGEGEPAAAHSDVLTEVEGPVDTAEASSDPHTEKLLEEQTCEAASETRSIEDKTRGEAAEARNEAAMPTADAGSTLPVIAIPGIMEDELEQTGAEAKDIPTE | ||||||
Modified residue | 72 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 109 | Asymmetric dimethylarginine; alternate | ||||
Sequence: R | ||||||
Modified residue | 109 | Omega-N-methylarginine; alternate | ||||
Sequence: R | ||||||
Modified residue | 199 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 232 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 276 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Cross-link | 314 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | ||||||
Modified residue | 320 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 325 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 336 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 552 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 659 | Phosphoserine | ||||
Sequence: S |
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
- PTM
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).
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
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9DBR0 | Fign Q9ERZ6 | 4 | EBI-4285802, EBI-11111349 | |
BINARY | Q9DBR0 | Nfkb1 P25799 | 4 | EBI-4285802, EBI-643958 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif, zinc finger.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-195 | Interaction with MCM2 | ||||
Sequence: MEQGYGGYGAWSAGPANTQGTYGSGMTSWQGYENYNYYNAQNTSVPAGTPYSYGPASWEATKTNDGGLAAGSPAMHVASFAPEPCTDNSDSLIAKINQRLDMLSKEGGRGGISSGGEGVQDRDSSFRFQPYESYDARPCIPEHNPYRPGYGYDYDFDLGTDRNGSFGGTFNDCRDPAPERGSLDGFLRGRGQGRF | ||||||
Region | 1-210 | Interaction with DPY30 | ||||
Sequence: MEQGYGGYGAWSAGPANTQGTYGSGMTSWQGYENYNYYNAQNTSVPAGTPYSYGPASWEATKTNDGGLAAGSPAMHVASFAPEPCTDNSDSLIAKINQRLDMLSKEGGRGGISSGGEGVQDRDSSFRFQPYESYDARPCIPEHNPYRPGYGYDYDFDLGTDRNGSFGGTFNDCRDPAPERGSLDGFLRGRGQGRFQDRSNSSTFIRSDPF | ||||||
Region | 105-124 | Disordered | ||||
Sequence: KEGGRGGISSGGEGVQDRDS | ||||||
Region | 109-201 | Interaction with DDX5 | ||||
Sequence: RGGISSGGEGVQDRDSSFRFQPYESYDARPCIPEHNPYRPGYGYDYDFDLGTDRNGSFGGTFNDCRDPAPERGSLDGFLRGRGQGRFQDRSNS | ||||||
Region | 185-218 | Disordered | ||||
Sequence: GFLRGRGQGRFQDRSNSSTFIRSDPFMPPSASEP | ||||||
Compositional bias | 194-218 | Polar residues | ||||
Sequence: RFQDRSNSSTFIRSDPFMPPSASEP | ||||||
Region | 277-379 | Disordered | ||||
Sequence: SQTRIRDWPRRRGFERFGPDNMGRKRKQFPLYEEPDAKLARADSDGDLSENDDGAGDLRSGDEEFRGEDDLCDSRKQRGEKEDEDEDVKKRREKQRRRDRMRD | ||||||
Compositional bias | 280-379 | Basic and acidic residues | ||||
Sequence: RIRDWPRRRGFERFGPDNMGRKRKQFPLYEEPDAKLARADSDGDLSENDDGAGDLRSGDEEFRGEDDLCDSRKQRGEKEDEDEDVKKRREKQRRRDRMRD | ||||||
Motif | 286-303 | Bipartite nuclear localization signal | ||||
Sequence: RRRGFERFGPDNMGRKRK | ||||||
Region | 384-447 | Involved in chromatin-binding | ||||
Sequence: RIQFACSVCKFRSFEDEEIQKHLQSKFHKETLRFISTKLPDKTVEFLQEYIINRNKKIEKRRQE | ||||||
Zinc finger | 389-411 | C2H2 AKAP95-type 1 | ||||
Sequence: CSVCKFRSFEDEEIQKHLQSKFH | ||||||
Zinc finger | 478-501 | C2H2 AKAP95-type 2 | ||||
Sequence: CLACDMLIPAQHQLLQRHLHSVDH | ||||||
Region | 522-565 | Involved in condensin complex recruitment | ||||
Sequence: SVLNNKHIVKMLEKYLKGEDPFVNETADLETEGDENVGEEKEET | ||||||
Region | 568-585 | RII-binding | ||||
Sequence: EVAAEVLAEVITAAVKAV | ||||||
Region | 572-589 | Required for interaction with MYCBP | ||||
Sequence: EVLAEVITAAVKAVEGEG | ||||||
Compositional bias | 624-645 | Basic and acidic residues | ||||
Sequence: QTCEAASETRSIEDKTRGEAAE | ||||||
Region | 624-659 | Disordered | ||||
Sequence: QTCEAASETRSIEDKTRGEAAEARNEAAMPTADAGS |
Sequence similarities
Belongs to the AKAP95 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length687
- Mass (Da)76,294
- Last updated2001-06-01 v1
- ChecksumBC1E320216A47E10
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A494B9I1 | A0A494B9I1_MOUSE | Akap8 | 361 | ||
A0A494B966 | A0A494B966_MOUSE | Akap8 | 60 | ||
A0A494B9L9 | A0A494B9L9_MOUSE | Akap8 | 82 | ||
A0A494B9W0 | A0A494B9W0_MOUSE | Akap8 | 55 | ||
A0A494BAT4 | A0A494BAT4_MOUSE | Akap8 | 71 | ||
A0A494BAG5 | A0A494BAG5_MOUSE | Akap8 | 59 | ||
A0A494BAZ0 | A0A494BAZ0_MOUSE | Akap8 | 148 |
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 194-218 | Polar residues | ||||
Sequence: RFQDRSNSSTFIRSDPFMPPSASEP | ||||||
Compositional bias | 280-379 | Basic and acidic residues | ||||
Sequence: RIRDWPRRRGFERFGPDNMGRKRKQFPLYEEPDAKLARADSDGDLSENDDGAGDLRSGDEEFRGEDDLCDSRKQRGEKEDEDEDVKKRREKQRRRDRMRD | ||||||
Sequence conflict | 323 | in Ref. 1; BAA84710 | ||||
Sequence: D → G | ||||||
Sequence conflict | 370 | in Ref. 1; BAA84710 | ||||
Sequence: K → E | ||||||
Sequence conflict | 541 | in Ref. 1; BAA84710 | ||||
Sequence: D → G | ||||||
Sequence conflict | 544 | in Ref. 1; BAA84710 | ||||
Sequence: V → A | ||||||
Sequence conflict | 584 | in Ref. 1; BAA84710 | ||||
Sequence: A → T | ||||||
Sequence conflict | 590 | in Ref. 1; BAA84710 | ||||
Sequence: E → G | ||||||
Compositional bias | 624-645 | Basic and acidic residues | ||||
Sequence: QTCEAASETRSIEDKTRGEAAE |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |