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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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri388 – 41225C2H2 AKAP95-type 1Add
BLAST
Zinc fingeri477 – 50226C2H2 AKAP95-type 2Add
BLAST

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
  • nucleoplasm Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi302 – 3032KR → EQ: Impairs nuclear localization. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 687687A-kinase anchor protein 8PRO_0000075383Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei72 – 721PhosphoserineBy similarity
Modified residuei321 – 3211PhosphoserineCombined sources
Modified residuei326 – 3261PhosphoserineCombined sources
Modified residuei337 – 3371PhosphoserineCombined sources
Modified residuei553 – 5531PhosphothreonineCombined sources
Modified residuei659 – 6591PhosphoserineCombined sources

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

Phosphoprotein

Proteomic databases

PaxDbiQ63014.
PRIDEiQ63014.

PTM databases

iPTMnetiQ63014.
PhosphoSiteiQ63014.

Expressioni

Tissue specificityi

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

Gene expression databases

ExpressionAtlasiQ63014. baseline.
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

GO - Molecular functioni

  • protein kinase A regulatory subunit binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000008827.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 210210Interaction with DPY30By similarityAdd
BLAST
Regioni1 – 195195Interaction with MCM2By similarityAdd
BLAST
Regioni109 – 20193Interaction with DDX51 PublicationAdd
BLAST
Regioni127 – 15226Nuclear matrix targeting site1 PublicationAdd
BLAST
Regioni385 – 44864Involved in chromatin-bindingBy similarityAdd
BLAST
Regioni523 – 56543Involved in condensin complex recruitmentBy similarityAdd
BLAST
Regioni568 – 58518RII-binding1 PublicationAdd
BLAST
Regioni572 – 58918Required for interaction with MYCBPBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi287 – 30418Bipartite nuclear localization signalBy similarity1 PublicationAdd
BLAST

Sequence similaritiesi

Belongs to the AKAP95 family.Curated
Contains 2 C2H2 AKAP95-type zinc fingers.Curated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri388 – 41225C2H2 AKAP95-type 1Add
BLAST
Zinc fingeri477 – 50226C2H2 AKAP95-type 2Add
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IFNG. Eukaryota.
ENOG410YE5A. LUCA.
GeneTreeiENSGT00530000063777.
HOGENOMiHOG000033876.
HOVERGENiHBG053198.
InParanoidiQ63014.
KOiK16525.
OMAiGCGRSQT.
OrthoDBiEOG741Z1X.
PhylomeDBiQ63014.
TreeFamiTF105407.

Family and domain databases

InterProiIPR007071. AKAP95.
[Graphical view]
PANTHERiPTHR12190. PTHR12190. 1 hit.
PfamiPF04988. AKAP95. 1 hit.
[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

STRINGi10116.ENSRNOP00000008827.

PTM databases

iPTMnetiQ63014.
PhosphoSiteiQ63014.

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.
OrthoDBiEOG741Z1X.
PhylomeDBiQ63014.
TreeFamiTF105407.

Miscellaneous databases

NextBioi619333.
PROiQ63014.

Gene expression databases

ExpressionAtlasiQ63014. baseline.
GenevisibleiQ63014. RN.

Family and domain databases

InterProiIPR007071. AKAP95.
[Graphical view]
PANTHERiPTHR12190. PTHR12190. 1 hit.
PfamiPF04988. AKAP95. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of AKAP 95, a nuclear protein that associates with the regulatory subunit of type II cAMP-dependent protein kinase."
    Coghlan V.M., Langeberg L.K., Fernandez A., Lamb N.J., Scott J.D.
    J. Biol. Chem. 269:7658-7665(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH PRKAR2A, RII-BINDING SITE.
    Tissue: Pituitary.
  2. "A-kinase-anchoring protein AKAP95 is targeted to the nuclear matrix and associates with p68 RNA helicase."
    Akileswaran L., Taraska J.W., Sayer J.A., Gettemy J.M., Coghlan V.M.
    J. Biol. Chem. 276:17448-17454(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH DDX5, NUCLEAR LOCALIZATION SIGNAL, MUTAGENESIS OF 302-LYS-ARG-303.
  3. "G1/S Cyclins interact with regulatory subunit of PKA via A-kinase anchoring protein, AKAP95."
    Arsenijevic T., Degraef C., Dumont J.E., Roger P.P., Pirson I.
    Cell Cycle 5:1217-1222(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CCNE1.
  4. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321; SER-326; SER-337; THR-553 AND SER-659, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

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: May 11, 2016
This is version 101 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.