AKAP8_RAT
ID AKAP8_RAT Reviewed; 687 AA.
AC Q63014;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=A-kinase anchor protein 8;
DE Short=AKAP-8;
DE AltName: Full=A-kinase anchor protein 95 kDa;
DE Short=AKAP 95;
GN Name=Akap8; Synonyms=Akap95;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INTERACTION WITH PRKAR2A, AND RII-BINDING SITE.
RC TISSUE=Pituitary;
RX PubMed=8125992; DOI=10.1016/s0021-9258(17)37338-6;
RA Coghlan V.M., Langeberg L.K., Fernandez A., Lamb N.J., Scott J.D.;
RT "Cloning and characterization of AKAP 95, a nuclear protein that associates
RT with the regulatory subunit of type II cAMP-dependent protein kinase.";
RL J. Biol. Chem. 269:7658-7665(1994).
RN [2]
RP SUBCELLULAR LOCATION, INTERACTION WITH DDX5, NUCLEAR LOCALIZATION SIGNAL,
RP AND MUTAGENESIS OF 302-LYS-ARG-303.
RX PubMed=11279182; DOI=10.1074/jbc.m101171200;
RA Akileswaran L., Taraska J.W., Sayer J.A., Gettemy J.M., Coghlan V.M.;
RT "A-kinase-anchoring protein AKAP95 is targeted to the nuclear matrix and
RT associates with p68 RNA helicase.";
RL J. Biol. Chem. 276:17448-17454(2001).
RN [3]
RP INTERACTION WITH CCNE1.
RX PubMed=16721056; DOI=10.4161/cc.5.11.2802;
RA Arsenijevic T., Degraef C., Dumont J.E., Roger P.P., Pirson I.;
RT "G1/S Cyclins interact with regulatory subunit of PKA via A-kinase
RT anchoring protein, AKAP95.";
RL Cell Cycle 5:1217-1222(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321; SER-326; SER-337;
RP THR-553 AND SER-659, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Anchoring protein that mediates the subcellular
CC compartmentation of cAMP-dependent protein kinase (PKA type II)
CC (PubMed:8125992). Acts as an anchor for a PKA-signaling complex onto
CC mitotic chromosomes, which is required for maintenance of chromosomes
CC in a condensed form throughout mitosis. Recruits condensin complex
CC subunit NCAPD2 to chromosomes required for chromatin condensation; the
CC function appears to be independent from PKA-anchoring. May help to
CC deliver cyclin D/E to CDK4 to facilitate cell cycle progression.
CC Required for cell cycle G2/M transition and histone deacetylation
CC during mitosis. In mitotic cells recruits HDAC3 to the vicinity of
CC chromatin leading to deacetylation and subsequent phosphorylation at
CC 'Ser-10' of histone H3; in this function may act redundantly with
CC AKAP8L. Involved in nuclear retention of RPS6KA1 upon ERK activation
CC thus inducing cell proliferation. May be involved in regulation of DNA
CC replication by acting as scaffold for MCM2. Enhances HMT activity of
CC the KMT2 family MLL4/WBP7 complex and is involved in transcriptional
CC regulation. In a teratocarcinoma cell line is involved in retinoic
CC acid-mediated induction of developmental genes implicating H3 'Lys-4'
CC methylation. May be involved in recruitment of active CASP3 to the
CC nucleus in apoptotic cells. May act as a carrier protein of GJA1 for
CC its transport to the nucleus. May play a repressive role in the
CC regulation of rDNA transcription. Preferentially binds GC-rich DNA in
CC vitro. In cells, associates with ribosomal RNA (rRNA) chromatin,
CC preferentially with rRNA promoter and transcribed regions. Involved in
CC modulation of Toll-like receptor signaling. Required for the cAMP-
CC dependent suppression of TNF-alpha in early stages of LPS-induced
CC macrophage activation; the function probably implicates targeting of
CC PKA to NFKB1 (By similarity). {ECO:0000250|UniProtKB:O43823,
CC ECO:0000250|UniProtKB:Q9DBR0, ECO:0000269|PubMed:8125992}.
CC -!- SUBUNIT: Binds to dimeric RII-alpha regulatory subunit of PKA during
CC mitosis (PubMed:8125992). Interacts (via C-terminus) with FIGN (By
CC similarity). Interacts with NCAPD2, CCND1, CCND3, MCM2, RPS6KA1, PDE4A,
CC CASP3 (By similarity). Interacts with DDX5, CCNE1 (PubMed:11279182,
CC PubMed:16721056). Interacts with NFKB1; detetcted in the cytoplasm.
CC Interacts with MYCBP; MYCBP is translocated to the nucleus and the
CC interaction prevents the association of the PKA catalytic subunit
CC leading to suppression of PKA activity. Interacts with DPY30; mediating
CC AKAP8 association with at least the MLL4/WBP7 HMT complex. Interacts
CC with HDAC3; increased during mitosis. Interacts with GJA1; in the
CC nucleus and in the nuclear membrane; the nuclear association increases
CC with progress of cell cycle G1, S and G2 phase and decreases in M phase
CC (By similarity). {ECO:0000250|UniProtKB:O43823,
CC ECO:0000250|UniProtKB:Q5VK71, ECO:0000250|UniProtKB:Q9DBR0,
CC ECO:0000269|PubMed:11279182, ECO:0000269|PubMed:16721056,
CC ECO:0000305|PubMed:8125992}.
CC -!- INTERACTION:
CC Q63014; Q61656: Ddx5; Xeno; NbExp=4; IntAct=EBI-11617845, EBI-643076;
CC -!- SUBCELLULAR LOCATION: Nucleus matrix {ECO:0000269|PubMed:11279182,
CC ECO:0000269|PubMed:8125992}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:O43823}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9DBR0}. Note=Associated with the nuclear
CC matrix. Redistributed and detached from condensed chromatin during
CC mitosis. Exhibits partial localization to the nucleolus in interphase,
CC possibly to the fibrillary center and/or to the dense fibrillary
CC component (By similarity). {ECO:0000250|UniProtKB:O43823}.
CC -!- TISSUE SPECIFICITY: Widely expressed. The protein has been detected in
CC liver, fibroblasts, granulosa, myoblast, lymphoma and Sertoli cells.
CC {ECO:0000269|PubMed:8125992}.
CC -!- PTM: Phosphorylated on tyrosine residues probably by SRC subfamily
CC protein kinases; multiple phosphorylation is leading to dissociation
CC from nuclear structures implicated in chromatin structural changes.
CC {ECO:0000250|UniProtKB:O43823}.
CC -!- SIMILARITY: Belongs to the AKAP95 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01140}.
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DR EMBL; U01914; AAA95941.1; -; mRNA.
DR RefSeq; NP_446307.1; NM_053855.1.
DR AlphaFoldDB; Q63014; -.
DR IntAct; Q63014; 1.
DR STRING; 10116.ENSRNOP00000008827; -.
DR iPTMnet; Q63014; -.
DR PhosphoSitePlus; Q63014; -.
DR jPOST; Q63014; -.
DR PaxDb; Q63014; -.
DR PRIDE; Q63014; -.
DR Ensembl; ENSRNOT00000008827; ENSRNOP00000008827; ENSRNOG00000006559.
DR GeneID; 116633; -.
DR KEGG; rno:116633; -.
DR UCSC; RGD:620832; rat.
DR CTD; 10270; -.
DR RGD; 620832; Akap8.
DR eggNOG; ENOG502QZY2; Eukaryota.
DR GeneTree; ENSGT00530000063777; -.
DR HOGENOM; CLU_024193_1_0_1; -.
DR InParanoid; Q63014; -.
DR OMA; EFCDSGR; -.
DR OrthoDB; 902224at2759; -.
DR PhylomeDB; Q63014; -.
DR TreeFam; TF105407; -.
DR PRO; PR:Q63014; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000006559; Expressed in spleen and 20 other tissues.
DR ExpressionAtlas; Q63014; baseline and differential.
DR Genevisible; Q63014; RN.
DR GO; GO:0000793; C:condensed chromosome; ISO:RGD.
DR GO; GO:0001939; C:female pronucleus; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0016363; C:nuclear matrix; IDA:RGD.
DR GO; GO:0005730; C:nucleolus; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; IDA:RGD.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:0051059; F:NF-kappaB binding; ISO:RGD.
DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; IDA:RGD.
DR GO; GO:0008270; F:zinc ion binding; IDA:RGD.
DR GO; GO:0044839; P:cell cycle G2/M phase transition; ISO:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; ISO:RGD.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0007076; P:mitotic chromosome condensation; ISO:RGD.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; ISO:RGD.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0033127; P:regulation of histone phosphorylation; ISO:RGD.
DR InterPro; IPR007071; AKAP95.
DR InterPro; IPR034736; ZF_C2H2_AKAP95.
DR PANTHER; PTHR12190; PTHR12190; 1.
DR Pfam; PF04988; AKAP95; 1.
DR PROSITE; PS51799; ZF_C2H2_AKAP95; 2.
PE 1: Evidence at protein level;
KW Cytoplasm; DNA-binding; Immunity; Innate immunity; Isopeptide bond;
KW Metal-binding; Methylation; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Transport; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..687
FT /note="A-kinase anchor protein 8"
FT /id="PRO_0000075383"
FT ZN_FING 390..412
FT /note="C2H2 AKAP95-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01140"
FT ZN_FING 479..502
FT /note="C2H2 AKAP95-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01140"
FT REGION 1..210
FT /note="Interaction with DPY30"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT REGION 1..195
FT /note="Interaction with MCM2"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT REGION 104..124
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 109..201
FT /note="Interaction with DDX5"
FT /evidence="ECO:0000269|PubMed:11279182"
FT REGION 127..152
FT /note="Nuclear matrix targeting site"
FT /evidence="ECO:0000305|PubMed:11279182"
FT REGION 189..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 278..380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 385..448
FT /note="Involved in chromatin-binding"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT REGION 523..565
FT /note="Involved in condensin complex recruitment"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT REGION 568..585
FT /note="RII-binding"
FT /evidence="ECO:0000305|PubMed:8125992"
FT REGION 572..589
FT /note="Required for interaction with MYCBP"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR0"
FT REGION 606..687
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 287..304
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:O43823,
FT ECO:0000269|PubMed:11279182"
FT COMPBIAS 194..221
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 281..380
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 629..644
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR0"
FT MOD_RES 109
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR0"
FT MOD_RES 109
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR0"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT MOD_RES 233
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR0"
FT MOD_RES 277
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 553
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 659
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CROSSLNK 315
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT CROSSLNK 563
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT MUTAGEN 302..303
FT /note="KR->EQ: Impairs nuclear localization."
FT /evidence="ECO:0000269|PubMed:11279182"
SQ SEQUENCE 687 AA; 76162 MW; 7535F30F18F1B8CB CRC64;
MEQSYGGYGA WSAGPANTQG TYGSGVASWQ GYENYSYYNA QNTSVPTGTP YSYGPASWEA
TKASDGGLAA GSSAMHVASF APEPCTDNSD SLIAKINQRL DMLSKEGGRG GISSGGEGMQ
DRDSSFRFQP YESYDSRPCM PEHTPYRPSY SYDYDFDLGT DRNGSFGGTF NDCRDPTPER
GALDGFLRGR GQGRFQDRSN SSTFIRSDPF MPPSASSEPL STTWSELNYM GGRGLGGPST
NRPPPSLFSQ SMAPDYSMMG MQGVGGFGGT MPYGCGRSQT RIRDWPRRRG FERFGPDNMG
RKRKPFPLYE EPDAKLARAD SEGDLSENDD GAGDLRSGDE EFRGEDDLCD SRKQRGEKED
EDEDVKKRRE KQRRRDRMRD RAADRIQFAC SVCKFRSFED EEIQKHLQSK FHKETLRFIS
TKLPDKTVEF LQEYIINRNK KIEKRRQELL EKESPKPKPD PFKGIGQEHF FKRIEAAHCL
ACDMLIPAQH QLLQRHLHSV DHNHNRRLAA EQFKKTSLHV AKSVLNNKHI VKMLEKYLKG
EDPFVNETAD LETEGDENLG EEKETPEEVA AEVLAEVITA AVKAVEGDGE PAAEHSDVLA
EVEGPVDTAE AGSDSHTGKL LEEQTCETAS ETRNMEDMAR GEAAEARNEA AVPAAAAGSP
VPVIAIPGIL EDELEQTDAE AKDTPTE
