{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"O43823","uniProtkbId":"AKAP8_HUMAN","entryAudit":{"firstPublicDate":"1999-07-15","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1998-06-01","entryVersion":206,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"A-kinase anchor protein 8"},"shortNames":[{"value":"AKAP-8"}]},"alternativeNames":[{"fullName":{"value":"A-kinase anchor protein 95 kDa"},"shortNames":[{"value":"AKAP 95"}]}]},"genes":[{"geneName":{"value":"AKAP8"},"synonyms":[{"value":"AKAP95"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q63014"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9DBR0"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10601332"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10791967"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11964380"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16980585"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22130794"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26683827"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26880274"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"14641107"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"9473338"}],"value":"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 in early stages of LPS-induced macrophage activation; the function probably implicates targeting of PKA to NFKB1 (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q5VK71"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q63014"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9DBR0"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10601332"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10764601"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11591814"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11964380"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12740381"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14641107"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15470020"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16980585"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22130794"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23995757"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26880274"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9473338"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"16227597"}],"value":"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; detected 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)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"O43823","intActId":"EBI-1237481"},"interactantTwo":{"uniProtKBAccession":"Q9UBL3","geneName":"ASH2L","intActId":"EBI-540797"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O43823","intActId":"EBI-1237481"},"interactantTwo":{"uniProtKBAccession":"P42574","geneName":"CASP3","intActId":"EBI-524064"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O43823","intActId":"EBI-1237481"},"interactantTwo":{"uniProtKBAccession":"Q9C005","geneName":"DPY30","intActId":"EBI-744973"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O43823","intActId":"EBI-1237481"},"interactantTwo":{"uniProtKBAccession":"O15379","geneName":"HDAC3","intActId":"EBI-607682"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O43823","intActId":"EBI-1237481"},"interactantTwo":{"uniProtKBAccession":"P49736","geneName":"MCM2","intActId":"EBI-374819"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O43823","intActId":"EBI-1237481"},"interactantTwo":{"uniProtKBAccession":"Q99417","geneName":"MYCBP","intActId":"EBI-716185"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O43823","intActId":"EBI-1237481"},"interactantTwo":{"uniProtKBAccession":"P13861","geneName":"PRKAR2A","intActId":"EBI-2556122"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O43823","intActId":"EBI-1237481"},"interactantTwo":{"uniProtKBAccession":"Q15418","geneName":"RPS6KA1","intActId":"EBI-963034"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"O43823","intActId":"EBI-1237481"},"interactantTwo":{"uniProtKBAccession":"P61964","geneName":"WDR5","intActId":"EBI-540834"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10601332"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26683827"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26880274"}],"value":"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"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19277197"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26683827"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10601332"}],"value":"Nucleus matrix","id":"SL-0181"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26683827"}],"value":"Nucleus, nucleolus","id":"SL-0188"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9DBR0"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19277197"}],"value":"Highly expressed in heart, liver, skeletal muscle, kidney and pancreas. Expressed in mature dendritic cells"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25770215"}],"value":"Phosphorylated on tyrosine residues probably by SRC subfamily protein kinases; multiple phosphorylation is leading to dissociation from nuclear structures implicated in chromatin structural changes"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01140"}],"value":"Belongs to the AKAP95 family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":692,"modifier":"EXACT"}},"description":"A-kinase anchor protein 8","featureId":"PRO_0000075381"},{"type":"Zinc finger","location":{"start":{"value":392,"modifier":"EXACT"},"end":{"value":414,"modifier":"EXACT"}},"description":"C2H2 AKAP95-type 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