AKAP8_HUMAN
ID AKAP8_HUMAN Reviewed; 692 AA.
AC O43823;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 187.
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH PRKAR2A, AND FUNCTION.
RC TISSUE=Cerebellum, and Testis;
RX PubMed=9473338; DOI=10.1006/excr.1997.3855;
RA Eide T., Coghlan V., Oerstavik S., Holsve C., Solberg R., Skaelhegg B.S.,
RA Lamb N.J.C., Langeberg L., Fernandez A., Scott J.D., Jahnsen T., Tasken K.;
RT "Molecular cloning, chromosomal localization, and cell cycle-dependent
RT subcellular distribution of the A-kinase anchoring protein, AKAP95.";
RL Exp. Cell Res. 238:305-316(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PRKAR2A AND NCAPD2.
RX PubMed=10601332; DOI=10.1083/jcb.147.6.1167;
RA Collas P., Le Guellec K., Tasken K.;
RT "The A-kinase-anchoring protein AKAP95 is a multivalent protein with a key
RT role in chromatin condensation at mitosis.";
RL J. Cell Biol. 147:1167-1180(1999).
RN [4]
RP FUNCTION.
RX PubMed=10791967; DOI=10.1083/jcb.149.3.531;
RA Steen R.L., Cubizolles F., Le Guellec K., Collas P.;
RT "A kinase-anchoring protein (AKAP)95 recruits human chromosome-associated
RT protein (hCAP)-D2/Eg7 for chromosome condensation in mitotic extract.";
RL J. Cell Biol. 149:531-536(2000).
RN [5]
RP INTERACTION WITH PRKAR2A.
RX PubMed=10764601; DOI=10.1006/jmbi.2000.3662;
RA Herberg F.W., Maleszka A., Eide T., Vossebein L., Tasken K.;
RT "Analysis of A-kinase anchoring protein (AKAP) interaction with protein
RT kinase A (PKA) regulatory subunits: PKA isoform specificity in AKAP
RT binding.";
RL J. Mol. Biol. 298:329-339(2000).
RN [6]
RP INTERACTION WITH PRKAR2A.
RX PubMed=11591814; DOI=10.1242/jcs.114.18.3255;
RA Landsverk H.B., Carlson C.R., Steen R.L., Vossebein L., Herberg F.W.,
RA Tasken K., Collas P.;
RT "Regulation of anchoring of the RIIalpha regulatory subunit of PKA to
RT AKAP95 by threonine phosphorylation of RIIalpha: implications for
RT chromosome dynamics at mitosis.";
RL J. Cell Sci. 114:3255-3264(2001).
RN [7]
RP FUNCTION, INTERACTION WITH NCAPD2, AND MUTAGENESIS OF ILE-582.
RX PubMed=11964380; DOI=10.1093/embo-reports/kvf089;
RA Eide T., Carlson C., Tasken K.A., Hirano T., Tasken K., Collas P.;
RT "Distinct but overlapping domains of AKAP95 are implicated in chromosome
RT condensation and condensin targeting.";
RL EMBO Rep. 3:426-432(2002).
RN [8]
RP FUNCTION, INTERACTION WITH MCM2, AND MUTAGENESIS OF ILE-582.
RX PubMed=12740381; DOI=10.1074/jbc.m300765200;
RA Eide T., Tasken K.A., Carlson C., Williams G., Jahnsen T., Tasken K.,
RA Collas P.;
RT "Protein kinase A-anchoring protein AKAP95 interacts with MCM2, a regulator
RT of DNA replication.";
RL J. Biol. Chem. 278:26750-26756(2003).
RN [9]
RP FUNCTION, AND INTERACTION WITH CCND1.
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).
RN [10]
RP INTERACTION WITH PDE4A.
RX PubMed=15470020; DOI=10.4049/jimmunol.173.8.4806;
RA Asirvatham A.L., Galligan S.G., Schillace R.V., Davey M.P., Vasta V.,
RA Beavo J.A., Carr D.W.;
RT "A-kinase anchoring proteins interact with phosphodiesterases in T
RT lymphocyte cell lines.";
RL J. Immunol. 173:4806-4814(2004).
RN [11]
RP FUNCTION, MUTAGENESIS OF ARG-290 AND 304-LYS-ARG-305, AND NUCLEAR
RP LOCALIZATION SIGNAL.
RX PubMed=16227597; DOI=10.1128/mcb.25.21.9469-9477.2005;
RA Kamada S., Kikkawa U., Tsujimoto Y., Hunter T.;
RT "A-kinase-anchoring protein 95 functions as a potential carrier for the
RT nuclear translocation of active caspase 3 through an enzyme-substrate-like
RT association.";
RL Mol. Cell. Biol. 25:9469-9477(2005).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323; SER-328 AND SER-339, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [13]
RP FUNCTION, AND INTERACTION WITH HDAC3.
RX PubMed=16980585; DOI=10.1101/gad.1455006;
RA Li Y., Kao G.D., Garcia B.A., Shabanowitz J., Hunt D.F., Qin J., Phelan C.,
RA Lazar M.A.;
RT "A novel histone deacetylase pathway regulates mitosis by modulating Aurora
RT B kinase activity.";
RL Genes Dev. 20:2566-2579(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-328, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323; SER-328 AND SER-339, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=19277197; DOI=10.1371/journal.pone.0004807;
RA Schillace R.V., Miller C.L., Pisenti N., Grotzke J.E., Swarbrick G.M.,
RA Lewinsohn D.M., Carr D.W.;
RT "A-kinase anchoring in dendritic cells is required for antigen
RT presentation.";
RL PLoS ONE 4:E4807-E4807(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323 AND SER-328, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323 AND SER-328, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112; SER-323; SER-328 AND
RP SER-339, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP FUNCTION, AND INTERACTION WITH RPS6KA1.
RX PubMed=22130794; DOI=10.1091/mbc.e11-07-0658;
RA Gao X., Chaturvedi D., Patel T.B.;
RT "Localization and retention of p90 ribosomal S6 kinase 1 in the nucleus:
RT implications for its function.";
RL Mol. Biol. Cell 23:503-515(2012).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-199; SER-323; SER-328 AND
RP SER-685, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [24]
RP FUNCTION, INTERACTION WITH DPY30, AND SUBUNIT.
RX PubMed=23995757; DOI=10.1038/nsmb.2656;
RA Jiang H., Lu X., Shimada M., Dou Y., Tang Z., Roeder R.G.;
RT "Regulation of transcription by the MLL2 complex and MLL complex-associated
RT AKAP95.";
RL Nat. Struct. Mol. Biol. 20:1156-1163(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-323 AND SER-328, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [26]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-277, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [27]
RP PHOSPHORYLATION.
RX PubMed=25770215; DOI=10.1074/jbc.m115.643882;
RA Kubota S., Morii M., Yuki R., Yamaguchi N., Yamaguchi H., Aoyama K.,
RA Kuga T., Tomonaga T., Yamaguchi N.;
RT "Role for tyrosine phosphorylation of a-kinase anchoring protein 8 (AKAP8)
RT in its dissociation from chromatin and the nuclear matrix.";
RL J. Biol. Chem. 290:10891-10904(2015).
RN [28]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26683827; DOI=10.1111/febs.13630;
RA Marstad A., Landsverk O.J., Stroemme O., Otterlei M., Collas P., Sundan A.,
RA Brede G.;
RT "A-kinase anchoring protein AKAP95 is a novel regulator of ribosomal RNA
RT synthesis.";
RL FEBS J. 283:757-770(2016).
RN [29]
RP INTERACTION WITH GJA1, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26880274; DOI=10.1038/srep21224;
RA Chen X., Kong X., Zhuang W., Teng B., Yu X., Hua S., Wang S., Liang F.,
RA Ma D., Zhang S., Zou X., Dai Y., Yang W., Zhang Y.;
RT "Dynamic changes in protein interaction between AKAP95 and Cx43 during cell
RT cycle progression of A549 cells.";
RL Sci. Rep. 6:21224-21224(2016).
RN [30]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-317 AND LYS-567, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [31]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-664.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Anchoring protein that mediates the subcellular
CC compartmentation of cAMP-dependent protein kinase (PKA type II)
CC (PubMed:9473338). 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 (PubMed:10601332,
CC PubMed:10791967, PubMed:11964380). May help to deliver cyclin D/E to
CC CDK4 to facilitate cell cycle progression (PubMed:14641107). Required
CC for cell cycle G2/M transition and histone deacetylation during
CC mitosis. In mitotic cells recruits HDAC3 to the vicinity of chromatin
CC leading to deacetylation and subsequent phosphorylation at 'Ser-10' of
CC histone H3; in this function may act redundantly with AKAP8L
CC (PubMed:16980585). Involved in nuclear retention of RPS6KA1 upon ERK
CC activation thus inducing cell proliferation (PubMed:22130794). May be
CC involved in regulation of DNA replication by acting as scaffold for
CC MCM2 (PubMed:12740381). Enhances HMT activity of the KMT2 family
CC MLL4/WBP7 complex and is involved in transcriptional regulation. In a
CC teratocarcinoma cell line is involved in retinoic acid-mediated
CC induction of developmental genes implicating H3 'Lys-4' methylation
CC (PubMed:23995757). May be involved in recruitment of active CASP3 to
CC the nucleus in apoptotic cells (PubMed:16227597). May act as a carrier
CC protein of GJA1 for its transport to the nucleus (PubMed:26880274). May
CC play a repressive role in the regulation of rDNA transcription.
CC Preferentially binds GC-rich DNA in vitro. In cells, associates with
CC ribosomal RNA (rRNA) chromatin, preferentially with rRNA promoter and
CC transcribed regions (PubMed:26683827). Involved in modulation of Toll-
CC like receptor signaling. Required for the cAMP-dependent suppression of
CC TNF-alpha in early stages of LPS-induced macrophage activation; the
CC function probably implicates targeting of PKA to NFKB1 (By similarity).
CC {ECO:0000250|UniProtKB:Q63014, ECO:0000250|UniProtKB:Q9DBR0,
CC ECO:0000269|PubMed:10601332, ECO:0000269|PubMed:10791967,
CC ECO:0000269|PubMed:11964380, ECO:0000269|PubMed:16980585,
CC ECO:0000269|PubMed:22130794, ECO:0000269|PubMed:26683827,
CC ECO:0000269|PubMed:26880274, ECO:0000305|PubMed:14641107,
CC ECO:0000305|PubMed:9473338}.
CC -!- SUBUNIT: Binds to the PKA RII-alpha regulatory subunit PRKAR2A
CC (phosphorylated at 'Thr-54') during mitosis (PubMed:9473338,
CC PubMed:10601332, PubMed:10764601, PubMed:11591814). Interacts (via C-
CC terminus) with FIGN (By similarity). Interacts with NCAPD2, CCND1,
CC MCM2, RPS6KA1, PDE4A (PubMed:10601332, PubMed:11964380,
CC PubMed:11591814, PubMed:12740381, PubMed:14641107, PubMed:15470020,
CC PubMed:22130794). Interacts with CCND3, CCNE1, DDX5, CASP3. Interacts
CC with NFKB1; detetcted in the cytoplasm. Interacts with MYCBP; MYCBP is
CC translocated to the nucleus and the interaction prevents the
CC association of the PKA catalytic subunit leading to suppression of PKA
CC activity (By similarity). Interacts with DPY30; mediating AKAP8
CC association with at least the MLL4/WBP7 HMT complex (PubMed:23995757).
CC Interacts with HDAC3; increased during mitosis (PubMed:16980585).
CC Interacts with GJA1; in the nucleus and in the nuclear membrane; the
CC nuclear association increases with progress of cell cycle G1, S and G2
CC phase and decreases in M phase (PubMed:26880274).
CC {ECO:0000250|UniProtKB:Q5VK71, ECO:0000250|UniProtKB:Q63014,
CC ECO:0000250|UniProtKB:Q9DBR0, ECO:0000269|PubMed:10601332,
CC ECO:0000269|PubMed:10764601, ECO:0000269|PubMed:11591814,
CC ECO:0000269|PubMed:11964380, ECO:0000269|PubMed:12740381,
CC ECO:0000269|PubMed:14641107, ECO:0000269|PubMed:15470020,
CC ECO:0000269|PubMed:16980585, ECO:0000269|PubMed:22130794,
CC ECO:0000269|PubMed:23995757, ECO:0000269|PubMed:26880274,
CC ECO:0000269|PubMed:9473338, ECO:0000305|PubMed:16227597}.
CC -!- INTERACTION:
CC O43823; Q9UBL3: ASH2L; NbExp=3; IntAct=EBI-1237481, EBI-540797;
CC O43823; P42574: CASP3; NbExp=5; IntAct=EBI-1237481, EBI-524064;
CC O43823; Q9C005: DPY30; NbExp=7; IntAct=EBI-1237481, EBI-744973;
CC O43823; O15379: HDAC3; NbExp=10; IntAct=EBI-1237481, EBI-607682;
CC O43823; P49736: MCM2; NbExp=7; IntAct=EBI-1237481, EBI-374819;
CC O43823; P13861: PRKAR2A; NbExp=3; IntAct=EBI-1237481, EBI-2556122;
CC O43823; Q15418: RPS6KA1; NbExp=5; IntAct=EBI-1237481, EBI-963034;
CC O43823; P61964: WDR5; NbExp=3; IntAct=EBI-1237481, EBI-540834;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19277197,
CC ECO:0000269|PubMed:26683827}. Nucleus matrix
CC {ECO:0000269|PubMed:10601332}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:26683827}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9DBR0}. Note=Associated with the nuclear matrix
CC in interphase and redistributes mostly to chromatin at mitosis.
CC However, mitotic chromatin localization has been questioned. Upon
CC nuclear reassembly at the end of mitosis, is sequestered into the
CC daughter nuclei where it re-acquires an interphase distribution.
CC Exhibits partial localization to the nucleolus in interphase, where it
CC colocalizes with UBTF/UBF, suggesting localization to the fibrillary
CC center and/or to the dense fibrillary component. Colocalizes with GJA1
CC at the nuclear membrane specifically during cell cycle G1/S phase.
CC {ECO:0000269|PubMed:10601332, ECO:0000269|PubMed:26683827,
CC ECO:0000269|PubMed:26880274}.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, liver, skeletal muscle,
CC kidney and pancreas. Expressed in mature dendritic cells.
CC {ECO:0000269|PubMed:19277197}.
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:0000269|PubMed:25770215}.
CC -!- SIMILARITY: Belongs to the AKAP95 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01140}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Y11997; CAA72722.1; -; mRNA.
DR EMBL; AC005785; AAC62838.1; -; Genomic_DNA.
DR CCDS; CCDS12329.1; -.
DR PIR; T13161; T13161.
DR RefSeq; NP_005849.1; NM_005858.3.
DR AlphaFoldDB; O43823; -.
DR BioGRID; 115561; 121.
DR DIP; DIP-38194N; -.
DR IntAct; O43823; 73.
DR MINT; O43823; -.
DR STRING; 9606.ENSP00000269701; -.
DR GlyGen; O43823; 4 sites, 2 O-linked glycans (4 sites).
DR iPTMnet; O43823; -.
DR MetOSite; O43823; -.
DR PhosphoSitePlus; O43823; -.
DR SwissPalm; O43823; -.
DR BioMuta; AKAP8; -.
DR EPD; O43823; -.
DR jPOST; O43823; -.
DR MassIVE; O43823; -.
DR MaxQB; O43823; -.
DR PaxDb; O43823; -.
DR PeptideAtlas; O43823; -.
DR PRIDE; O43823; -.
DR ProteomicsDB; 49189; -.
DR Antibodypedia; 1427; 356 antibodies from 36 providers.
DR DNASU; 10270; -.
DR Ensembl; ENST00000269701.7; ENSP00000269701.1; ENSG00000105127.10.
DR GeneID; 10270; -.
DR KEGG; hsa:10270; -.
DR MANE-Select; ENST00000269701.7; ENSP00000269701.1; NM_005858.4; NP_005849.1.
DR UCSC; uc002nav.4; human.
DR CTD; 10270; -.
DR DisGeNET; 10270; -.
DR GeneCards; AKAP8; -.
DR HGNC; HGNC:378; AKAP8.
DR HPA; ENSG00000105127; Low tissue specificity.
DR MIM; 604692; gene.
DR neXtProt; NX_O43823; -.
DR OpenTargets; ENSG00000105127; -.
DR PharmGKB; PA24672; -.
DR VEuPathDB; HostDB:ENSG00000105127; -.
DR eggNOG; ENOG502QZY2; Eukaryota.
DR GeneTree; ENSGT00530000063777; -.
DR HOGENOM; CLU_024193_1_0_1; -.
DR InParanoid; O43823; -.
DR OMA; EFCDSGR; -.
DR OrthoDB; 902224at2759; -.
DR PhylomeDB; O43823; -.
DR TreeFam; TF105407; -.
DR PathwayCommons; O43823; -.
DR SignaLink; O43823; -.
DR SIGNOR; O43823; -.
DR BioGRID-ORCS; 10270; 11 hits in 1092 CRISPR screens.
DR ChiTaRS; AKAP8; human.
DR GeneWiki; AKAP8; -.
DR GenomeRNAi; 10270; -.
DR Pharos; O43823; Tbio.
DR PRO; PR:O43823; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O43823; protein.
DR Bgee; ENSG00000105127; Expressed in sural nerve and 195 other tissues.
DR ExpressionAtlas; O43823; baseline and differential.
DR Genevisible; O43823; HS.
DR GO; GO:0000793; C:condensed chromosome; IEA:Ensembl.
DR GO; GO:0001939; C:female pronucleus; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0016363; C:nuclear matrix; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:CACAO.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003690; F:double-stranded DNA binding; IEA:Ensembl.
DR GO; GO:0042826; F:histone deacetylase binding; IDA:UniProtKB.
DR GO; GO:0051059; F:NF-kappaB binding; IEA:Ensembl.
DR GO; GO:0034237; F:protein kinase A regulatory subunit binding; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:Ensembl.
DR GO; GO:0044839; P:cell cycle G2/M phase transition; IMP:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:ProtInc.
DR GO; GO:0007076; P:mitotic chromosome condensation; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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..692
FT /note="A-kinase anchor protein 8"
FT /id="PRO_0000075381"
FT ZN_FING 392..414
FT /note="C2H2 AKAP95-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01140"
FT ZN_FING 481..504
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:0000269|PubMed:23995757"
FT REGION 1..195
FT /note="Interaction with MCM2"
FT /evidence="ECO:0000269|PubMed:12740381"
FT REGION 109..201
FT /note="Interaction with DDX5"
FT /evidence="ECO:0000250|UniProtKB:Q63014"
FT REGION 168..203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 231..254
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 387..450
FT /note="Involved in chromatin-binding"
FT /evidence="ECO:0000269|PubMed:11964380"
FT REGION 525..569
FT /note="Involved in condensin complex recruitment"
FT /evidence="ECO:0000269|PubMed:11964380"
FT REGION 545..571
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 592..692
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 289..306
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q63014,
FT ECO:0000305|PubMed:16227597"
FT COMPBIAS 279..382
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 112
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 199
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
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:0007744|PubMed:24129315"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63014"
FT MOD_RES 685
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 317
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 567
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 664
FT /note="Q -> H (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036534"
FT MUTAGEN 290
FT /note="R->S: No nuclear localization; when associated with
FT 304-N-S-305."
FT /evidence="ECO:0000269|PubMed:16227597"
FT MUTAGEN 304..305
FT /note="KR->NS: No nuclear localization; when associated
FT with S-290."
FT /evidence="ECO:0000269|PubMed:16227597"
FT MUTAGEN 392
FT /note="C->S: Abolishes chromosome-condensation activity;
FT when associated with S-395."
FT /evidence="ECO:0000269|PubMed:11964380"
FT MUTAGEN 395
FT /note="C->S: Abolishes chromosome-condensation activity;
FT when associated with S-392."
FT /evidence="ECO:0000269|PubMed:11964380"
FT MUTAGEN 481
FT /note="C->S: Abolishes chromosome-condensation activity and
FT recruitment of condensin complex; when associated with S-
FT 484."
FT /evidence="ECO:0000269|PubMed:11964380"
FT MUTAGEN 484
FT /note="C->S: Abolishes chromosome-condensation activity and
FT recruitment of condensin complex; when associated with S-
FT 481."
FT /evidence="ECO:0000269|PubMed:11964380"
FT MUTAGEN 582
FT /note="I->P: No effect on activity to regulate DNA
FT replication and on condensin complex recruitment."
FT /evidence="ECO:0000269|PubMed:11964380,
FT ECO:0000269|PubMed:12740381"
SQ SEQUENCE 692 AA; 76108 MW; CBCD5F014FD94B66 CRC64;
MDQGYGGYGA WSAGPANTQG AYGTGVASWQ GYENYNYYGA QNTSVTTGAT YSYGPASWEA
AKANDGGLAA GAPAMHMASY GPEPCTDNSD SLIAKINQRL DMMSKEGGRG GSGGGGEGIQ
DRESSFRFQP FESYDSRPCL PEHNPYRPSY SYDYEFDLGS DRNGSFGGQY SECRDPARER
GSLDGFMRGR GQGRFQDRSN PGTFMRSDPF VPPAASSEPL STPWNELNYV GGRGLGGPSP
SRPPPSLFSQ SMAPDYGVMG MQGAGGYDST MPYGCGRSQP RMRDRDRPKR RGFDRFGPDG
TGRKRKQFQL YEEPDTKLAR VDSEGDFSEN DDAAGDFRSG DEEFKGEDEL CDSGRQRGEK
EDEDEDVKKR REKQRRRDRT RDRAADRIQF ACSVCKFRSF DDEEIQKHLQ SKFHKETLRF
ISTKLPDKTV EFLQEYIVNR NKKIEKRRQE LMEKETAKPK PDPFKGIGQE HFFKKIEAAH
CLACDMLIPA QPQLLQRHLH SVDHNHNRRL AAEQFKKTSL HVAKSVLNNR HIVKMLEKYL
KGEDPFTSET VDPEMEGDDN LGGEDKKETP EEVAADVLAE VITAAVRAVD GEGAPAPESS
GEPAEDEGPT DTAEAGSDPQ AEQLLEEQVP CGTAHEKGVP KARSEAAEAG NGAETMAAEA
ESAQTRVAPA PAAADAEVEQ TDAESKDAVP TE
