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Protein

A-kinase anchor protein 8

Gene

Akap8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity). Specifically involved in recruitment of CAPD2 to, and condensation of maternal but not paternal chromosomes (PubMed:12082153). 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. 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. Seems to involved in modulation of rDNA transcription. Preferentially binds GC-rich DNA in vitro and associates to GC-rich ribosomal RNA promoters (By similarity). 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 (PubMed:19531803).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri389 – 411C2H2 AKAP95-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri478 – 501C2H2 AKAP95-type 2PROSITE-ProRule annotationAdd BLAST24

GO - Molecular functioni

GO - Biological processi

  • cell cycle G2/M phase transition Source: MGI
  • cellular response to lipopolysaccharide Source: UniProtKB
  • cellular response to prostaglandin E stimulus Source: UniProtKB
  • innate immune response Source: UniProtKB-KW
  • mitotic chromosome condensation Source: MGI
  • negative regulation of tumor necrosis factor production Source: UniProtKB
  • positive regulation of histone deacetylation Source: MGI
  • protein transport Source: UniProtKB-KW
  • regulation of histone phosphorylation Source: MGI
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Immunity, Innate immunity, Protein transport, Transcription, Transcription regulation, Transport

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
A-kinase anchor protein 8
Short name:
AKAP-8
Alternative name(s):
A-kinase anchor protein 95 kDa
Short name:
AKAP 95
Gene namesi
Name:Akap8
Synonyms:Akap95
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:1928488. Akap8.

Subcellular locationi

  • Nucleus matrix 1 Publication
  • Nucleusnucleolus By similarity
  • Cytoplasm 1 Publication

  • Note: Associated with the nuclear matrix. Redistributed and detached from condensed chromatin during mitosis (By similarity). Localizes specifically to the vicinity of the meiotic spindle in metaphase II oocytes.By similarity1 Publication

GO - Cellular componenti

  • condensed chromosome Source: MGI
  • female pronucleus Source: MGI
  • Golgi apparatus Source: Ensembl
  • membrane Source: MGI
  • mitochondrion Source: Ensembl
  • nuclear chromatin Source: MGI
  • nuclear matrix Source: UniProtKB
  • nucleolus Source: UniProtKB-SubCell
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

AKAP8 and FIGN double mutant mice die soon after birth due to cleft palate.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000753821 – 687A-kinase anchor protein 8Add BLAST687

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei72PhosphoserineCombined sources1
Modified residuei109Asymmetric dimethylarginine; alternateCombined sources1
Modified residuei109Omega-N-methylarginine; alternateCombined sources1
Modified residuei199PhosphoserineBy similarity1
Modified residuei232Omega-N-methylarginineCombined sources1
Modified residuei276Omega-N-methylarginineCombined sources1
Modified residuei320PhosphoserineCombined sources1
Modified residuei325PhosphoserineCombined sources1
Modified residuei336PhosphoserineCombined sources1
Modified residuei552PhosphothreonineBy similarity1
Modified residuei659PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on tyrosine residues probably by SRC subfamily protein kinases; multiple phosphorylation is leading to dissociation from nuclear structures implicated in chromatin structural changes.By similarity

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ9DBR0.
MaxQBiQ9DBR0.
PaxDbiQ9DBR0.
PRIDEiQ9DBR0.

PTM databases

iPTMnetiQ9DBR0.
PhosphoSitePlusiQ9DBR0.

Expressioni

Developmental stagei

Weakly expressed in metaphase II oocytes. Strongly up-regulated after fertilization at the pronuclear stage and restricted to the female pronucleus. Subsequently localized to the nucleus of each blastomere and on condensed chromosomes in mitotic cells.1 Publication

Gene expression databases

BgeeiENSMUSG00000024045.
CleanExiMM_AKAP8.
ExpressionAtlasiQ9DBR0. baseline and differential.
GenevisibleiQ9DBR0. MM.

Interactioni

Subunit structurei

Binds to the PKA RII-alpha regulatory subunit PRKAR2A (By similarity). Interacts (via C-terminus) with FIGN (PubMed:16751186). Interacts with NCAPD2, CCND3, CCNE1, MCM2, RPS6KA1, DDX5, PDE4A (By similarity). 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 (PubMed:12414807). Interacts with CCND1, CASP3 (PubMed:14641107, PubMed:16227597). Interacts with NFKB1; detetcted in the cytoplasm (PubMed:19531803). Interacts with DPY30; mediating AKAP8 association with at least the MLL4/WBP7 HMT complex. Interacts with HDAC3; increased during mitosis. 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 (By similarity).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FignQ9ERZ64EBI-4285802,EBI-11111349
Nfkb1P257994EBI-4285802,EBI-643958

GO - Molecular functioni

Protein-protein interaction databases

BioGridi207953. 19 interactors.
IntActiQ9DBR0. 25 interactors.
MINTiMINT-4128362.
STRINGi10090.ENSMUSP00000002699.

Structurei

3D structure databases

ProteinModelPortaliQ9DBR0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 210Interaction with DPY30By similarityAdd BLAST210
Regioni1 – 195Interaction with MCM2By similarityAdd BLAST195
Regioni109 – 201Interaction with DDX5By similarityAdd BLAST93
Regioni384 – 447Involved in chromatin-bindingBy similarityAdd BLAST64
Regioni522 – 565Involved in condensin complex recruitmentBy similarityAdd BLAST44
Regioni568 – 585RII-bindingBy similarityAdd BLAST18
Regioni572 – 589Required for interaction with MYCBP1 PublicationAdd BLAST18

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi286 – 303Bipartite nuclear localization signalBy similarityAdd BLAST18

Sequence similaritiesi

Belongs to the AKAP95 family.PROSITE-ProRule annotation
Contains 2 C2H2 AKAP95-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri389 – 411C2H2 AKAP95-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri478 – 501C2H2 AKAP95-type 2PROSITE-ProRule annotationAdd BLAST24

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IFNG. Eukaryota.
ENOG410YE5A. LUCA.
GeneTreeiENSGT00530000063777.
HOGENOMiHOG000033876.
HOVERGENiHBG053198.
InParanoidiQ9DBR0.
KOiK16525.
OMAiGCGRSQT.
OrthoDBiEOG091G0836.
PhylomeDBiQ9DBR0.
TreeFamiTF105407.

Family and domain databases

InterProiIPR007071. AKAP95.
[Graphical view]
PANTHERiPTHR12190. PTHR12190. 1 hit.
PfamiPF04988. AKAP95. 1 hit.
[Graphical view]
PROSITEiPS51799. ZF_C2H2_AKAP95. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9DBR0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEQGYGGYGA WSAGPANTQG TYGSGMTSWQ GYENYNYYNA QNTSVPAGTP
60 70 80 90 100
YSYGPASWEA TKTNDGGLAA GSPAMHVASF APEPCTDNSD SLIAKINQRL
110 120 130 140 150
DMLSKEGGRG GISSGGEGVQ DRDSSFRFQP YESYDARPCI PEHNPYRPGY
160 170 180 190 200
GYDYDFDLGT DRNGSFGGTF NDCRDPAPER GSLDGFLRGR GQGRFQDRSN
210 220 230 240 250
SSTFIRSDPF MPPSASEPLS TTWNELNYMG GRGLGGPSTS RPPPSLFSQS
260 270 280 290 300
MAPDYSMMGM QGVGGFGGTM PYGCGRSQTR IRDWPRRRGF ERFGPDNMGR
310 320 330 340 350
KRKQFPLYEE PDAKLARADS DGDLSENDDG AGDLRSGDEE FRGEDDLCDS
360 370 380 390 400
RKQRGEKEDE DEDVKKRREK QRRRDRMRDR AADRIQFACS VCKFRSFEDE
410 420 430 440 450
EIQKHLQSKF HKETLRFIST KLPDKTVEFL QEYIINRNKK IEKRRQELLE
460 470 480 490 500
KESPKPKPDP FKGIGQEHFF KKIEAAHCLA CDMLIPAQHQ LLQRHLHSVD
510 520 530 540 550
HNHNRRLAAE QFKKTSLHVA KSVLNNKHIV KMLEKYLKGE DPFVNETADL
560 570 580 590 600
ETEGDENVGE EKEETPEEVA AEVLAEVITA AVKAVEGEGE PAAAHSDVLT
610 620 630 640 650
EVEGPVDTAE ASSDPHTEKL LEEQTCEAAS ETRSIEDKTR GEAAEARNEA
660 670 680
AMPTADAGST LPVIAIPGIM EDELEQTGAE AKDIPTE
Length:687
Mass (Da):76,294
Last modified:June 1, 2001 - v1
Checksum:iBC1E320216A47E10
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti323D → G in BAA84710 (Ref. 1) Curated1
Sequence conflicti370K → E in BAA84710 (Ref. 1) Curated1
Sequence conflicti541D → G in BAA84710 (Ref. 1) Curated1
Sequence conflicti544V → A in BAA84710 (Ref. 1) Curated1
Sequence conflicti584A → T in BAA84710 (Ref. 1) Curated1
Sequence conflicti590E → G in BAA84710 (Ref. 1) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB028920 mRNA. Translation: BAA84710.1.
AK004801 mRNA. Translation: BAB23574.1.
AK089092 mRNA. Translation: BAC40746.1.
CCDSiCCDS37555.1.
RefSeqiNP_062748.2. NM_019774.5.
UniGeneiMm.328945.

Genome annotation databases

EnsembliENSMUST00000002699; ENSMUSP00000002699; ENSMUSG00000024045.
GeneIDi56399.
KEGGimmu:56399.
UCSCiuc008bwg.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB028920 mRNA. Translation: BAA84710.1.
AK004801 mRNA. Translation: BAB23574.1.
AK089092 mRNA. Translation: BAC40746.1.
CCDSiCCDS37555.1.
RefSeqiNP_062748.2. NM_019774.5.
UniGeneiMm.328945.

3D structure databases

ProteinModelPortaliQ9DBR0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207953. 19 interactors.
IntActiQ9DBR0. 25 interactors.
MINTiMINT-4128362.
STRINGi10090.ENSMUSP00000002699.

PTM databases

iPTMnetiQ9DBR0.
PhosphoSitePlusiQ9DBR0.

Proteomic databases

EPDiQ9DBR0.
MaxQBiQ9DBR0.
PaxDbiQ9DBR0.
PRIDEiQ9DBR0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000002699; ENSMUSP00000002699; ENSMUSG00000024045.
GeneIDi56399.
KEGGimmu:56399.
UCSCiuc008bwg.2. mouse.

Organism-specific databases

CTDi10270.
MGIiMGI:1928488. Akap8.

Phylogenomic databases

eggNOGiENOG410IFNG. Eukaryota.
ENOG410YE5A. LUCA.
GeneTreeiENSGT00530000063777.
HOGENOMiHOG000033876.
HOVERGENiHBG053198.
InParanoidiQ9DBR0.
KOiK16525.
OMAiGCGRSQT.
OrthoDBiEOG091G0836.
PhylomeDBiQ9DBR0.
TreeFamiTF105407.

Miscellaneous databases

ChiTaRSiAkap8. mouse.
PROiQ9DBR0.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024045.
CleanExiMM_AKAP8.
ExpressionAtlasiQ9DBR0. baseline and differential.
GenevisibleiQ9DBR0. MM.

Family and domain databases

InterProiIPR007071. AKAP95.
[Graphical view]
PANTHERiPTHR12190. PTHR12190. 1 hit.
PfamiPF04988. AKAP95. 1 hit.
[Graphical view]
PROSITEiPS51799. ZF_C2H2_AKAP95. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAKAP8_MOUSE
AccessioniPrimary (citable) accession number: Q9DBR0
Secondary accession number(s): Q9R0L8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: June 1, 2001
Last modified: November 30, 2016
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.