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Protein

A-kinase anchor protein 8

Gene

Akap8

Organism
Rattus norvegicus (Rat)
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) (PubMed:8125992). 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. May help to deliver cyclin D/E to CDK4 to facilitate cell cycle progression. 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. 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 (By similarity).By similarity1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri390 – 412C2H2 AKAP95-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri479 – 502C2H2 AKAP95-type 2PROSITE-ProRule annotationAdd BLAST24

GO - Molecular functioni

  • DNA binding Source: RGD
  • double-stranded DNA binding Source: RGD
  • poly(A) RNA binding Source: Ensembl
  • protein kinase A regulatory subunit binding Source: RGD
  • zinc ion binding Source: RGD

GO - Biological processi

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi620832. Akap8.

Subcellular locationi

  • Nucleus matrix 2 Publications
  • Nucleusnucleolus By similarity
  • Cytoplasm By similarity

  • Note: Associated with the nuclear matrix. Redistributed and detached from condensed chromatin during mitosis.

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi302 – 303KR → EQ: Impairs nuclear localization. 1 Publication2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000753831 – 687A-kinase anchor protein 8Add BLAST687

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei72PhosphoserineBy similarity1
Modified residuei109Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei109Omega-N-methylarginine; alternateBy similarity1
Modified residuei199PhosphoserineBy similarity1
Modified residuei233Omega-N-methylarginineBy similarity1
Modified residuei277Omega-N-methylarginineBy similarity1
Modified residuei321PhosphoserineCombined sources1
Modified residuei326PhosphoserineCombined sources1
Modified residuei337PhosphoserineCombined sources1
Modified residuei553PhosphothreonineCombined sources1
Modified residuei659PhosphoserineCombined sources1

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

PaxDbiQ63014.
PRIDEiQ63014.

PTM databases

iPTMnetiQ63014.
PhosphoSitePlusiQ63014.

Expressioni

Tissue specificityi

Widely expressed. The protein has been detected in liver, fibroblasts, granulosa, myoblast, lymphoma and Sertoli cells.1 Publication

Gene expression databases

BgeeiENSRNOG00000006559.
ExpressionAtlasiQ63014. differential.
GenevisibleiQ63014. RN.

Interactioni

Subunit structurei

Binds to dimeric RII-alpha regulatory subunit of PKA during mitosis (PubMed:8125992). Interacts (via C-terminus) with FIGN (By similarity). Interacts with NCAPD2, CCND1, CCND3, MCM2, RPS6KA1, PDE4A, CASP3 (By similarity). Interacts with DDX5, CCNE1 (PubMed:11279182, PubMed:16721056). Interacts with NFKB1; detetcted 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. 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 similarity1 Publication2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ddx5Q616564EBI-11617845,EBI-643076From a different organism.

GO - Molecular functioni

  • protein kinase A regulatory subunit binding Source: RGD

Protein-protein interaction databases

IntActiQ63014. 1 interactor.
STRINGi10116.ENSRNOP00000008827.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 210Interaction with DPY30By similarityAdd BLAST210
Regioni1 – 195Interaction with MCM2By similarityAdd BLAST195
Regioni109 – 201Interaction with DDX51 PublicationAdd BLAST93
Regioni127 – 152Nuclear matrix targeting site1 PublicationAdd BLAST26
Regioni385 – 448Involved in chromatin-bindingBy similarityAdd BLAST64
Regioni523 – 565Involved in condensin complex recruitmentBy similarityAdd BLAST43
Regioni568 – 585RII-binding1 PublicationAdd BLAST18
Regioni572 – 589Required for interaction with MYCBPBy similarityAdd BLAST18

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi287 – 304Bipartite nuclear localization signalBy similarity1 PublicationAdd 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 fingeri390 – 412C2H2 AKAP95-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri479 – 502C2H2 AKAP95-type 2PROSITE-ProRule annotationAdd BLAST24

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IFNG. Eukaryota.
ENOG410YE5A. LUCA.
GeneTreeiENSGT00530000063777.
HOGENOMiHOG000033876.
HOVERGENiHBG053198.
InParanoidiQ63014.
KOiK16525.
OMAiGCGRSQT.
OrthoDBiEOG091G0836.
PhylomeDBiQ63014.
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.

Q63014-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEQSYGGYGA WSAGPANTQG TYGSGVASWQ GYENYSYYNA QNTSVPTGTP
60 70 80 90 100
YSYGPASWEA TKASDGGLAA GSSAMHVASF APEPCTDNSD SLIAKINQRL
110 120 130 140 150
DMLSKEGGRG GISSGGEGMQ DRDSSFRFQP YESYDSRPCM PEHTPYRPSY
160 170 180 190 200
SYDYDFDLGT DRNGSFGGTF NDCRDPTPER GALDGFLRGR GQGRFQDRSN
210 220 230 240 250
SSTFIRSDPF MPPSASSEPL STTWSELNYM GGRGLGGPST NRPPPSLFSQ
260 270 280 290 300
SMAPDYSMMG MQGVGGFGGT MPYGCGRSQT RIRDWPRRRG FERFGPDNMG
310 320 330 340 350
RKRKPFPLYE EPDAKLARAD SEGDLSENDD GAGDLRSGDE EFRGEDDLCD
360 370 380 390 400
SRKQRGEKED EDEDVKKRRE KQRRRDRMRD RAADRIQFAC SVCKFRSFED
410 420 430 440 450
EEIQKHLQSK FHKETLRFIS TKLPDKTVEF LQEYIINRNK KIEKRRQELL
460 470 480 490 500
EKESPKPKPD PFKGIGQEHF FKRIEAAHCL ACDMLIPAQH QLLQRHLHSV
510 520 530 540 550
DHNHNRRLAA EQFKKTSLHV AKSVLNNKHI VKMLEKYLKG EDPFVNETAD
560 570 580 590 600
LETEGDENLG EEKETPEEVA AEVLAEVITA AVKAVEGDGE PAAEHSDVLA
610 620 630 640 650
EVEGPVDTAE AGSDSHTGKL LEEQTCETAS ETRNMEDMAR GEAAEARNEA
660 670 680
AVPAAAAGSP VPVIAIPGIL EDELEQTDAE AKDTPTE
Length:687
Mass (Da):76,162
Last modified:November 1, 1996 - v1
Checksum:i7535F30F18F1B8CB
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U01914 mRNA. Translation: AAA95941.1.
RefSeqiNP_446307.1. NM_053855.1.
UniGeneiRn.10248.

Genome annotation databases

EnsembliENSRNOT00000008827; ENSRNOP00000008827; ENSRNOG00000006559.
GeneIDi116633.
KEGGirno:116633.
UCSCiRGD:620832. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U01914 mRNA. Translation: AAA95941.1.
RefSeqiNP_446307.1. NM_053855.1.
UniGeneiRn.10248.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ63014. 1 interactor.
STRINGi10116.ENSRNOP00000008827.

PTM databases

iPTMnetiQ63014.
PhosphoSitePlusiQ63014.

Proteomic databases

PaxDbiQ63014.
PRIDEiQ63014.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000008827; ENSRNOP00000008827; ENSRNOG00000006559.
GeneIDi116633.
KEGGirno:116633.
UCSCiRGD:620832. rat.

Organism-specific databases

CTDi10270.
RGDi620832. Akap8.

Phylogenomic databases

eggNOGiENOG410IFNG. Eukaryota.
ENOG410YE5A. LUCA.
GeneTreeiENSGT00530000063777.
HOGENOMiHOG000033876.
HOVERGENiHBG053198.
InParanoidiQ63014.
KOiK16525.
OMAiGCGRSQT.
OrthoDBiEOG091G0836.
PhylomeDBiQ63014.
TreeFamiTF105407.

Miscellaneous databases

PROiQ63014.

Gene expression databases

BgeeiENSRNOG00000006559.
ExpressionAtlasiQ63014. differential.
GenevisibleiQ63014. RN.

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_RAT
AccessioniPrimary (citable) accession number: Q63014
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 106 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. 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.