Protein: A-kinase anchor protein 8 (AKAP-8) (A-kinase anchor protein 95 kDa) (AKAP 95) (O43823)
Organism: Homo sapiens (Human)
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 {ECO:0000269|PubMed:19277197, ECO:0000269|PubMed:26683827}. Nucleus matrix {ECO:0000269|PubMed:10601332}. Nucleus, nucleolus {ECO:0000269|PubMed:26683827}. Cytoplasm {ECO:0000250|UniProtKB:Q9DBR0}. 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. {ECO:0000269|PubMed:10601332, ECO:0000269|PubMed:26683827, ECO:0000269|PubMed:26880274}.
InterPro domains:
- IPR034736: Zinc finger C2H2 AKAP95-type (domain) [392-504]
- IPR007071: A-kinase anchoring protein 95 (AKAP95) (family) [1-661]
Sequence:
MDQGYGGYGAWSAGPANTQGAYGTGVASWQGYENYNYYGAQNTSVTTGATYSYGPASWEAAKANDGGLAAGAPAMHMASYGPEPCTDNSDSLIAKINQRLDMMSKEGGRGGSGGGGEGIQDRESSFRFQPFESYDSRPCLPEHNPYRPSYSYDYEFDLGSDRNGSFGGQYSECRDPARERGSLDGFMRGRGQGRFQDRSNPGTFMRSDPFVPPAASSEPLSTPWNELNYVGGRGLGGPSPSRPPPSLFSQSMAPDYGVMGMQGAGGYDSTMPYGCGRSQPRMRDRDRPKRRGFDRFGPDGTGRKRKQFQLYEEPDTKLARVDSEGDFSENDDAAGDFRSGDEEFKGEDELCDSGRQRGEKEDEDEDVKKRREKQRRRDRTRDRAADRIQFACSVCKFRSFDDEEIQKHLQSKFHKETLRFISTKLPDKTVEFLQEYIVNRNKKIEKRRQELMEKETAKPKPDPFKGIGQEHFFKKIEAAHCLACDMLIPAQPQLLQRHLHSVDHNHNRRLAAEQFKKTSLHVAKSVLNNRHIVKMLEKYLKGEDPFTSETVDPEMEGDDNLGGEDKKETPEEVAADVLAEVITAAVRAVDGEGAPAPESSGEPAEDEGPTDTAEAGSDPQAEQLLEEQVPCGTAHEKGVPKARSEAAEAGNGAETMAAEAESAQTRVAPAPAAADAEVEQTDAESKDAVPTE
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0097159 (organic cyclic compound binding), GO:0043167 (ion binding), GO:1901363 (heterocyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0043169 (cation binding), GO:0051018 (protein kinase A binding), GO:0003677 (DNA binding), GO:0046872 (metal ion binding), GO:0034237 (protein kinase A regulatory subunit binding), GO:0046914 (transition metal ion binding), GO:0003690 (double-stranded DNA binding), GO:0008270 (zinc ion binding)
Biological Process (BP): GO:0008150 (biological process), GO:0050789 (regulation of biological process), GO:0065007 (biological regulation), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0019222 (regulation of metabolic process), GO:0071840 (cellular component organization or biogenesis), GO:0009892 (negative regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0048523 (negative regulation of cellular process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0044085 (cellular component biogenesis), GO:0060255 (regulation of macromolecule metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0016043 (cellular component organization), GO:0031323 (regulation of cellular metabolic process), GO:0009890 (negative regulation of biosynthetic process), GO:0080090 (regulation of primary metabolic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0022613 (ribonucleoprotein complex biogenesis), GO:0010468 (regulation of gene expression), GO:0022607 (cellular component assembly), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0010558 (negative regulation of macromolecule biosynthetic process), GO:0031327 (negative regulation of cellular biosynthetic process), GO:0051252 (regulation of RNA metabolic process), GO:0043933 (protein-containing complex organization), GO:0051253 (negative regulation of RNA metabolic process), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0065003 (protein-containing complex assembly), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0022618 (ribonucleoprotein complex assembly), GO:1902679 (negative regulation of RNA biosynthetic process), GO:0071826 (ribonucleoprotein complex subunit organization), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0045892 (negative regulation of DNA-templated transcription), GO:1903507 (negative regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0000122 (negative regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0016363 (nuclear matrix), GO:0016604 (nuclear body), GO:1990904 (ribonucleoprotein complex), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0000785 (chromatin), GO:0034399 (nuclear periphery), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0016607 (nuclear speck), GO:0043227 (membrane-bounded organelle), GO:0043228 (non-membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0031981 (nuclear lumen), GO:0005694 (chromosome), GO:0005634 (nucleus)