Protein: A-kinase anchor protein 8 (AKAP-8) (A-kinase anchor protein 95 kDa) (AKAP 95) (Q63014)
Organism: Rattus norvegicus (Rat)
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. May help to deliver cyclin D/E to CDK4 to facilitate cell cycle progression. 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. 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).
Subcellular location: Nucleus matrix {ECO:0000269|PubMed:11279182, ECO:0000269|PubMed:8125992}. Nucleus, nucleolus {ECO:0000250|UniProtKB:O43823}. Cytoplasm {ECO:0000250|UniProtKB:Q9DBR0}. Note=Associated with the nuclear matrix. Redistributed and detached from condensed chromatin during mitosis. Exhibits partial localization to the nucleolus in interphase, possibly to the fibrillary center and/or to the dense fibrillary component (By similarity). {ECO:0000250|UniProtKB:O43823}.
Interaction partners:
- A-kinase anchor protein 11
- A-kinase anchor protein 10, mitochondrial
- A-kinase anchor protein 1, mitochondrial
Sequence:
MEQSYGGYGAWSAGPANTQGTYGSGVASWQGYENYSYYNAQNTSVPTGTPYSYGPASWEATKASDGGLAAGSSAMHVASFAPEPCTDNSDSLIAKINQRLDMLSKEGGRGGISSGGEGMQDRDSSFRFQPYESYDSRPCMPEHTPYRPSYSYDYDFDLGTDRNGSFGGTFNDCRDPTPERGALDGFLRGRGQGRFQDRSNSSTFIRSDPFMPPSASSEPLSTTWSELNYMGGRGLGGPSTNRPPPSLFSQSMAPDYSMMGMQGVGGFGGTMPYGCGRSQTRIRDWPRRRGFERFGPDNMGRKRKPFPLYEEPDAKLARADSEGDLSENDDGAGDLRSGDEEFRGEDDLCDSRKQRGEKEDEDEDVKKRREKQRRRDRMRDRAADRIQFACSVCKFRSFEDEEIQKHLQSKFHKETLRFISTKLPDKTVEFLQEYIINRNKKIEKRRQELLEKESPKPKPDPFKGIGQEHFFKRIEAAHCLACDMLIPAQHQLLQRHLHSVDHNHNRRLAAEQFKKTSLHVAKSVLNNKHIVKMLEKYLKGEDPFVNETADLETEGDENLGEEKETPEEVAAEVLAEVITAAVKAVEGDGEPAAEHSDVLAEVEGPVDTAEAGSDSHTGKLLEEQTCETASETRNMEDMARGEAAEARNEAAVPAAAAGSPVPVIAIPGILEDELEQTDAEAKDTPTE