AKAP8_CANLF
ID AKAP8_CANLF Reviewed; 698 AA.
AC Q5VK71;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 25-MAY-2022, entry version 88.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH CCND3.
RX PubMed=14641107; DOI=10.1042/bj20031765;
RA Arsenijevic T., Degraef C., Dumont J.E., Roger P.P., Pirson I.;
RT "A novel partner for D-type cyclins: protein kinase A-anchoring protein
RT AKAP95.";
RL Biochem. J. 378:673-679(2004).
CC -!- FUNCTION: Anchoring protein that mediates the subcellular
CC compartmentation of cAMP-dependent protein kinase (PKA type II). Acts
CC as an anchor for a PKA-signaling complex onto mitotic chromosomes,
CC which is required for maintenance of chromosomes in a condensed form
CC throughout mitosis. Recruits condensin complex subunit NCAPD2 to
CC chromosomes required for chromatin condensation; the function appears
CC to be independent from PKA-anchoring. May help to deliver cyclin D/E to
CC CDK4 to facilitate cell cycle progression. Required for cell cycle G2/M
CC transition and histone deacetylation during mitosis. In mitotic cells
CC recruits HDAC3 to the vicinity of chromatin leading to deacetylation
CC and subsequent phosphorylation at 'Ser-10' of histone H3; in this
CC function may act redundantly with AKAP8L. Involved in nuclear retention
CC of RPS6KA1 upon ERK activation thus inducing cell proliferation. May be
CC involved in regulation of DNA replication by acting as scaffold for
CC MCM2. Enhances HMT activity of the KMT2 family MLL4/WBP7 complex and is
CC involved in transcriptional regulation. In a teratocarcinoma cell line
CC is involved in retinoic acid-mediated induction of developmental genes
CC implicating H3 'Lys-4' methylation. May be involved in recruitment of
CC active CASP3 to the nucleus in apoptotic cells. May act as a carrier
CC protein of GJA1 for its transport to the nucleus. May play a repressive
CC role in the regulation of rDNA transcription. Preferentially binds GC-
CC rich DNA in vitro. In cells, associates with ribosomal RNA (rRNA)
CC chromatin, preferentially with rRNA promoter and transcribed regions.
CC Involved in modulation of Toll-like receptor signaling. Required for
CC the cAMP-dependent suppression of TNF-alpha in early stages of LPS-
CC induced macrophage activation; the function probably implicates
CC targeting of PKA to NFKB1 (By similarity).
CC {ECO:0000250|UniProtKB:O43823, ECO:0000250|UniProtKB:Q63014,
CC ECO:0000250|UniProtKB:Q9DBR0}.
CC -!- SUBUNIT: Binds to dimeric RII-alpha regulatory subunit of PKA during
CC mitosis. Interacts (via C-terminus) with FIGN. Interacts with CCND3
CC (PubMed:14641107). Interacts with NCAPD2, CCND1, MCM2, RPS6KA1, PDE4A,
CC CASP3, DDX5, CCNE1. 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:Q63014, ECO:0000250|UniProtKB:Q9DBR0,
CC ECO:0000269|PubMed:14641107}.
CC -!- INTERACTION:
CC Q5VK71; P30281: CCND3; Xeno; NbExp=6; IntAct=EBI-11601938, EBI-375013;
CC Q5VK71; P24864: CCNE1; Xeno; NbExp=2; IntAct=EBI-11601938, EBI-519526;
CC -!- SUBCELLULAR LOCATION: Nucleus matrix {ECO:0000250|UniProtKB:Q63014}.
CC Nucleus, nucleolus {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 ECO:0000250|UniProtKB:Q63014}.
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; AY382602; AAQ84303.1; -; mRNA.
DR RefSeq; NP_001007124.1; NM_001007123.1.
DR AlphaFoldDB; Q5VK71; -.
DR IntAct; Q5VK71; 6.
DR STRING; 9615.ENSCAFP00000041643; -.
DR PaxDb; Q5VK71; -.
DR PRIDE; Q5VK71; -.
DR GeneID; 474362; -.
DR KEGG; cfa:474362; -.
DR CTD; 10270; -.
DR eggNOG; ENOG502QZY2; Eukaryota.
DR InParanoid; Q5VK71; -.
DR OrthoDB; 902224at2759; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016363; C:nuclear matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
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..698
FT /note="A-kinase anchor protein 8"
FT /id="PRO_0000064533"
FT ZN_FING 393..415
FT /note="C2H2 AKAP95-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01140"
FT ZN_FING 482..505
FT /note="C2H2 AKAP95-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01140"
FT REGION 1..213
FT /note="Interaction with DPY30"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT REGION 1..198
FT /note="Interaction with MCM2"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT REGION 102..123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 108..204
FT /note="Interaction with DDX5"
FT /evidence="ECO:0000250|UniProtKB:Q63014"
FT REGION 126..151
FT /note="Nuclear matrix targeting site"
FT /evidence="ECO:0000250|UniProtKB:Q63014"
FT REGION 161..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 388..451
FT /note="Involved in chromatin-binding"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT REGION 526..569
FT /note="Involved in condensin complex recruitment"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT REGION 546..570
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 572..589
FT /note="RII-binding"
FT /evidence="ECO:0000250|UniProtKB:Q63014"
FT REGION 576..593
FT /note="Required for interaction with MYCBP"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR0"
FT REGION 591..698
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 290..307
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:O43823,
FT ECO:0000250|UniProtKB:Q63014"
FT MOTIF 369..378
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 195..213
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 288..383
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 550..566
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 108
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR0"
FT MOD_RES 108
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR0"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT MOD_RES 236
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9DBR0"
FT MOD_RES 280
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT MOD_RES 324
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O43823"
FT CROSSLNK 318
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O43823"
SQ SEQUENCE 698 AA; 76839 MW; B714D7E7E1731382 CRC64;
MEQGYGGYGA WSAGPTNTQG AYGTGVASWQ GYENYNYYGA QNTSVTTGAS YSYGPASWET
TKASDSLGAG GPAVHMASYG PEPCTDNSDS LIAKINQRLD MMSKEGGRGG SSGGGEGMQD
RESSFRFQSY ESYDSRSCLP EHHPYRPSYS YDYDFDPMPD RNGGFSSQYG DCRDPARERG
SLDGFMRGRG QGQGQGRFQD RSNPSTFMRS DPFMPPSASS EPLSAPWPEL NYVGGRGLGG
PSPSRPPPSL FSQSMAPDFG VMGMQGAGGY DNSVPYGCGR SQTRMRDRPR RRGFDRCGPD
GMGRKRKQLQ IYDEPDAKLA RADSEGDFSE NDDGAADFRS GDEEFRGEDE FFDPGRQRGE
KDDEDDEVKK RREKQRRRDR MRDRAADRIQ FACSVCKFRS FEDEEIQKHL QSKFHKETLR
FISTKLPDKT VEFLQEYIVN RNKKIEKRRQ ELMEKESTKP KPDPFKGIGQ EHFFKKIEAA
HCLACDMLIP AQHQLLQRHL HSVDHNHNRR LAAEQFKKTS LHVARSVLNN RHIVKMLEKY
LKGEDPFTSE AVDPEIEGDD TLGGEKEETP EEVAAEVLAE VITAAVRAVD GEGAPAPEGS
DTPPEGQGPV DTAEATHSPH SEQLVEVETP CGAAPEKGDA NAEAGGETTE AAGEEQEVVA
KTDGAVDGTV RGAAPAPPVT ETKAEQTEAE PKDVTPTE
