O43823 · AKAP8_HUMAN
- ProteinA-kinase anchor protein 8
- GeneAKAP8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids692 (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) (PubMed:9473338).
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 (PubMed:10601332, PubMed:10791967, PubMed:11964380).
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 (PubMed:16980585).
Involved in nuclear retention of RPS6KA1 upon ERK activation thus inducing cell proliferation (PubMed:22130794).
May be involved in regulation of DNA replication by acting as scaffold for MCM2 (PubMed:12740381).
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 (PubMed:23995757).
May be involved in recruitment of active CASP3 to the nucleus in apoptotic cells (PubMed:16227597).
May act as a carrier protein of GJA1 for its transport to the nucleus (PubMed:26880274).
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 (PubMed:26683827).
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 (By similarity).
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 (PubMed:10601332, PubMed:10791967, PubMed:11964380).
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 (PubMed:16980585).
Involved in nuclear retention of RPS6KA1 upon ERK activation thus inducing cell proliferation (PubMed:22130794).
May be involved in regulation of DNA replication by acting as scaffold for MCM2 (PubMed:12740381).
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 (PubMed:23995757).
May be involved in recruitment of active CASP3 to the nucleus in apoptotic cells (PubMed:16227597).
May act as a carrier protein of GJA1 for its transport to the nucleus (PubMed:26880274).
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 (PubMed:26683827).
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 (By similarity).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | condensed chromosome | |
Cellular Component | cytoplasm | |
Cellular Component | female pronucleus | |
Cellular Component | membrane | |
Cellular Component | nuclear matrix | |
Cellular Component | nucleolus | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
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 | RNA 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 cell cycle | |
Biological Process | mitotic chromosome condensation | |
Biological Process | negative regulation of tumor necrosis factor production | |
Biological Process | protein transport | |
Biological Process | signal transduction |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameA-kinase anchor protein 8
- Short namesAKAP-8
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO43823
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Associated with the nuclear matrix in interphase and redistributes mostly to chromatin at mitosis. However, mitotic chromatin localization has been questioned. Upon nuclear reassembly at the end of mitosis, is sequestered into the daughter nuclei where it re-acquires an interphase distribution. Exhibits partial localization to the nucleolus in interphase, where it colocalizes with UBTF/UBF, suggesting localization to the fibrillary center and/or to the dense fibrillary component. Colocalizes with GJA1 at the nuclear membrane specifically during cell cycle G1/S phase.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 290 | No nuclear localization; when associated with 304-N-S-305. | ||||
Sequence: R → S | ||||||
Mutagenesis | 304-305 | No nuclear localization; when associated with S-290. | ||||
Sequence: KR → NS | ||||||
Mutagenesis | 392 | Abolishes chromosome-condensation activity; when associated with S-395. | ||||
Sequence: C → S | ||||||
Mutagenesis | 395 | Abolishes chromosome-condensation activity; when associated with S-392. | ||||
Sequence: C → S | ||||||
Mutagenesis | 481 | Abolishes chromosome-condensation activity and recruitment of condensin complex; when associated with S-484. | ||||
Sequence: C → S | ||||||
Mutagenesis | 484 | Abolishes chromosome-condensation activity and recruitment of condensin complex; when associated with S-481. | ||||
Sequence: C → S | ||||||
Mutagenesis | 582 | No effect on activity to regulate DNA replication and on condensin complex recruitment. | ||||
Sequence: I → P | ||||||
Natural variant | VAR_036534 | 664 | in a breast cancer sample; somatic mutation | |||
Sequence: Q → H |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 897 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data), cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000075381 | 1-692 | UniProt | A-kinase anchor protein 8 | |||
Sequence: MDQGYGGYGAWSAGPANTQGAYGTGVASWQGYENYNYYGAQNTSVTTGATYSYGPASWEAAKANDGGLAAGAPAMHMASYGPEPCTDNSDSLIAKINQRLDMMSKEGGRGGSGGGGEGIQDRESSFRFQPFESYDSRPCLPEHNPYRPSYSYDYEFDLGSDRNGSFGGQYSECRDPARERGSLDGFMRGRGQGRFQDRSNPGTFMRSDPFVPPAASSEPLSTPWNELNYVGGRGLGGPSPSRPPPSLFSQSMAPDYGVMGMQGAGGYDSTMPYGCGRSQPRMRDRDRPKRRGFDRFGPDGTGRKRKQFQLYEEPDTKLARVDSEGDFSENDDAAGDFRSGDEEFKGEDELCDSGRQRGEKEDEDEDVKKRREKQRRRDRTRDRAADRIQFACSVCKFRSFDDEEIQKHLQSKFHKETLRFISTKLPDKTVEFLQEYIVNRNKKIEKRRQELMEKETAKPKPDPFKGIGQEHFFKKIEAAHCLACDMLIPAQPQLLQRHLHSVDHNHNRRLAAEQFKKTSLHVAKSVLNNRHIVKMLEKYLKGEDPFTSETVDPEMEGDDNLGGEDKKETPEEVAADVLAEVITAAVRAVDGEGAPAPESSGEPAEDEGPTDTAEAGSDPQAEQLLEEQVPCGTAHEKGVPKARSEAAEAGNGAETMAAEAESAQTRVAPAPAAADAEVEQTDAESKDAVPTE | |||||||
Modified residue | 109 | UniProt | Asymmetric dimethylarginine; alternate | ||||
Sequence: R | |||||||
Modified residue | 109 | UniProt | Omega-N-methylarginine; alternate | ||||
Sequence: R | |||||||
Modified residue | 112 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 112 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 165 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 199 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 233 | UniProt | Omega-N-methylarginine | ||||
Sequence: R | |||||||
Modified residue | 277 | UniProt | Omega-N-methylarginine | ||||
Sequence: R | |||||||
Cross-link | 317 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue | 323 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 323 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 328 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 328 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 339 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 339 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 353 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 399 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 567 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 644 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 662 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 681 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 685 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 685 | PRIDE | 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
Tissue specificity
Highly expressed in heart, liver, skeletal muscle, kidney and pancreas. Expressed in mature dendritic cells.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Binds to the PKA RII-alpha regulatory subunit PRKAR2A (phosphorylated at 'Thr-54') during mitosis (PubMed:10601332, PubMed:10764601, PubMed:11591814, PubMed:9473338).
Interacts (via C-terminus) with FIGN (By similarity).
Interacts with NCAPD2, CCND1, MCM2, RPS6KA1, PDE4A (PubMed:10601332, PubMed:11591814, PubMed:11964380, PubMed:12740381, PubMed:14641107, PubMed:15470020, PubMed:22130794).
Interacts with CCND3, CCNE1, DDX5, CASP3. Interacts with NFKB1; detetcted in the cytoplasm. 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 (By similarity).
Interacts with DPY30; mediating AKAP8 association with at least the MLL4/WBP7 HMT complex (PubMed:23995757).
Interacts with HDAC3; increased during mitosis (PubMed:16980585).
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 (PubMed:26880274).
Interacts (via C-terminus) with FIGN (By similarity).
Interacts with NCAPD2, CCND1, MCM2, RPS6KA1, PDE4A (PubMed:10601332, PubMed:11591814, PubMed:11964380, PubMed:12740381, PubMed:14641107, PubMed:15470020, PubMed:22130794).
Interacts with CCND3, CCNE1, DDX5, CASP3. Interacts with NFKB1; detetcted in the cytoplasm. 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 (By similarity).
Interacts with DPY30; mediating AKAP8 association with at least the MLL4/WBP7 HMT complex (PubMed:23995757).
Interacts with HDAC3; increased during mitosis (PubMed:16980585).
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 (PubMed:26880274).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O43823 | ASH2L Q9UBL3 | 3 | EBI-1237481, EBI-540797 | |
BINARY | O43823 | CASP3 P42574 | 5 | EBI-1237481, EBI-524064 | |
BINARY | O43823 | DPY30 Q9C005 | 7 | EBI-1237481, EBI-744973 | |
BINARY | O43823 | HDAC3 O15379 | 10 | EBI-1237481, EBI-607682 | |
BINARY | O43823 | MCM2 P49736 | 7 | EBI-1237481, EBI-374819 | |
BINARY | O43823 | MYCBP Q99417 | 3 | EBI-1237481, EBI-716185 | |
BINARY | O43823 | PRKAR2A P13861 | 3 | EBI-1237481, EBI-2556122 | |
BINARY | O43823 | RPS6KA1 Q15418 | 5 | EBI-1237481, EBI-963034 | |
BINARY | O43823 | WDR5 P61964 | 3 | EBI-1237481, EBI-540834 |
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: MDQGYGGYGAWSAGPANTQGAYGTGVASWQGYENYNYYGAQNTSVTTGATYSYGPASWEAAKANDGGLAAGAPAMHMASYGPEPCTDNSDSLIAKINQRLDMMSKEGGRGGSGGGGEGIQDRESSFRFQPFESYDSRPCLPEHNPYRPSYSYDYEFDLGSDRNGSFGGQYSECRDPARERGSLDGFMRGRGQGRF | ||||||
Region | 1-210 | Interaction with DPY30 | ||||
Sequence: MDQGYGGYGAWSAGPANTQGAYGTGVASWQGYENYNYYGAQNTSVTTGATYSYGPASWEAAKANDGGLAAGAPAMHMASYGPEPCTDNSDSLIAKINQRLDMMSKEGGRGGSGGGGEGIQDRESSFRFQPFESYDSRPCLPEHNPYRPSYSYDYEFDLGSDRNGSFGGQYSECRDPARERGSLDGFMRGRGQGRFQDRSNPGTFMRSDPF | ||||||
Region | 109-201 | Interaction with DDX5 | ||||
Sequence: RGGSGGGGEGIQDRESSFRFQPFESYDSRPCLPEHNPYRPSYSYDYEFDLGSDRNGSFGGQYSECRDPARERGSLDGFMRGRGQGRFQDRSNP | ||||||
Region | 168-203 | Disordered | ||||
Sequence: GQYSECRDPARERGSLDGFMRGRGQGRFQDRSNPGT | ||||||
Region | 231-254 | Disordered | ||||
Sequence: GGRGLGGPSPSRPPPSLFSQSMAP | ||||||
Region | 269-382 | Disordered | ||||
Sequence: STMPYGCGRSQPRMRDRDRPKRRGFDRFGPDGTGRKRKQFQLYEEPDTKLARVDSEGDFSENDDAAGDFRSGDEEFKGEDELCDSGRQRGEKEDEDEDVKKRREKQRRRDRTRD | ||||||
Compositional bias | 279-382 | Basic and acidic residues | ||||
Sequence: QPRMRDRDRPKRRGFDRFGPDGTGRKRKQFQLYEEPDTKLARVDSEGDFSENDDAAGDFRSGDEEFKGEDELCDSGRQRGEKEDEDEDVKKRREKQRRRDRTRD | ||||||
Motif | 289-306 | Bipartite nuclear localization signal | ||||
Sequence: KRRGFDRFGPDGTGRKRK | ||||||
Region | 387-450 | Involved in chromatin-binding | ||||
Sequence: RIQFACSVCKFRSFDDEEIQKHLQSKFHKETLRFISTKLPDKTVEFLQEYIVNRNKKIEKRRQE | ||||||
Zinc finger | 392-414 | C2H2 AKAP95-type 1 | ||||
Sequence: CSVCKFRSFDDEEIQKHLQSKFH | ||||||
Zinc finger | 481-504 | C2H2 AKAP95-type 2 | ||||
Sequence: CLACDMLIPAQPQLLQRHLHSVDH | ||||||
Region | 525-569 | Involved in condensin complex recruitment | ||||
Sequence: SVLNNRHIVKMLEKYLKGEDPFTSETVDPEMEGDDNLGGEDKKET | ||||||
Region | 545-571 | Disordered | ||||
Sequence: PFTSETVDPEMEGDDNLGGEDKKETPE | ||||||
Region | 572-589 | RII-binding | ||||
Sequence: EVAADVLAEVITAAVRAV | ||||||
Region | 576-593 | Required for interaction with MYCBP | ||||
Sequence: DVLAEVITAAVRAVDGEG | ||||||
Region | 592-692 | Disordered | ||||
Sequence: EGAPAPESSGEPAEDEGPTDTAEAGSDPQAEQLLEEQVPCGTAHEKGVPKARSEAAEAGNGAETMAAEAESAQTRVAPAPAAADAEVEQTDAESKDAVPTE |
Sequence similarities
Belongs to the AKAP95 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length692
- Mass (Da)76,108
- Last updated1998-06-01 v1
- ChecksumCBCD5F014FD94B66
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A7P0T893 | A0A7P0T893_HUMAN | AKAP8 | 679 | ||
A0A7P0TBC8 | A0A7P0TBC8_HUMAN | AKAP8 | 372 | ||
A0A7P0TAA4 | A0A7P0TAA4_HUMAN | AKAP8 | 133 | ||
M0QX51 | M0QX51_HUMAN | AKAP8 | 364 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 279-382 | Basic and acidic residues | ||||
Sequence: QPRMRDRDRPKRRGFDRFGPDGTGRKRKQFQLYEEPDTKLARVDSEGDFSENDDAAGDFRSGDEEFKGEDELCDSGRQRGEKEDEDEDVKKRREKQRRRDRTRD |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Y11997 EMBL· GenBank· DDBJ | CAA72722.1 EMBL· GenBank· DDBJ | mRNA | ||
AC005785 EMBL· GenBank· DDBJ | AAC62838.1 EMBL· GenBank· DDBJ | Genomic DNA |