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Protein

A-kinase anchor protein 8

Gene

AKAP8

Organism
Homo sapiens (Human)
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:9473338). 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 (PubMed:10601332, PubMed:10791967, PubMed:11964380). 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 (PubMed:16980585). Involved in nuclear retention of RPS6KA1 upon ERK activation thus inducing cell proliferation (PubMed:22130794). May be involved in regulation of DNA replication by acting as scaffold for MCM2 (PubMed:12740381). 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 (PubMed:23995757). May be involved in recruitment of active CASP3 to the nucleus in apoptotic cells (PubMed:16227597). May act as a carrier protein of GJA1 for its transport to the nucleus (PubMed:26880274). Seems to involved in modulation of rDNA transcription. Preferentially binds GC-rich DNA in vitro and associates to GC-rich ribosomal RNA promoters (PubMed:26683827). 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 similarity2 Publications7 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri392 – 414C2H2 AKAP95-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri481 – 504C2H2 AKAP95-type 2PROSITE-ProRule annotationAdd BLAST24

GO - Molecular functioni

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

GO - Biological processi

  • cell cycle G2/M phase transition Source: UniProtKB
  • cellular response to lipopolysaccharide Source: Ensembl
  • cellular response to prostaglandin E stimulus Source: Ensembl
  • innate immune response Source: UniProtKB-KW
  • mitotic chromosome condensation Source: Ensembl
  • mitotic nuclear division Source: ProtInc
  • negative regulation of tumor necrosis factor production Source: Ensembl
  • positive regulation of histone deacetylation Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of histone phosphorylation Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • signal transduction Source: ProtInc
  • 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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105127-MONOMER.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:378. AKAP8.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi290R → S: No nuclear localization; when associated with 304-N-S-305. 1 Publication1
Mutagenesisi304 – 305KR → NS: No nuclear localization; when associated with S-290. 1 Publication2
Mutagenesisi392C → S: Abolishes chromosome-condensation activity; when associated with S-395. 1 Publication1
Mutagenesisi395C → S: Abolishes chromosome-condensation activity; when associated with S-392. 1 Publication1
Mutagenesisi481C → S: Abolishes chromosome-condensation activity and recruitment of condensin complex; when associated with S-484. 1 Publication1
Mutagenesisi484C → S: Abolishes chromosome-condensation activity and recruitment of condensin complex; when associated with S-481. 1 Publication1
Mutagenesisi582I → P: No effect on activity to regulate DNA replication and on condensin complex recruitment. 2 Publications1

Organism-specific databases

OpenTargetsiENSG00000105127.
PharmGKBiPA24672.

Polymorphism and mutation databases

BioMutaiAKAP8.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000753811 – 692A-kinase anchor protein 8Add BLAST692

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei109Asymmetric dimethylarginine; alternateBy similarity1
Modified residuei109Omega-N-methylarginine; alternateBy similarity1
Modified residuei112PhosphoserineCombined sources1
Modified residuei199PhosphoserineCombined sources1
Modified residuei233Omega-N-methylarginineBy similarity1
Modified residuei277Omega-N-methylarginineCombined sources1
Modified residuei323PhosphoserineCombined sources1
Modified residuei328PhosphoserineCombined sources1
Modified residuei339PhosphoserineCombined sources1
Modified residuei662PhosphoserineBy similarity1
Modified residuei685PhosphoserineCombined 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.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiO43823.
MaxQBiO43823.
PaxDbiO43823.
PeptideAtlasiO43823.
PRIDEiO43823.

PTM databases

iPTMnetiO43823.
PhosphoSitePlusiO43823.
SwissPalmiO43823.

Expressioni

Tissue specificityi

Highly expressed in heart, liver, skeletal muscle, kidney and pancreas. Expressed in mature dendritic cells.1 Publication

Gene expression databases

BgeeiENSG00000105127.
CleanExiHS_AKAP8.
ExpressionAtlasiO43823. baseline and differential.
GenevisibleiO43823. HS.

Organism-specific databases

HPAiHPA004776.

Interactioni

Subunit structurei

Binds to the PKA RII-alpha regulatory subunit PRKAR2A (phosphorylated at 'Thr-54') during mitosis (PubMed:9473338, PubMed:10601332, PubMed:10764601, PubMed:11591814). Interacts (via C-terminus) with FIGN (By similarity). Interacts with NCAPD2, CCND1, MCM2, RPS6KA1, PDE4A (PubMed:10601332, PubMed:11964380, PubMed:11591814, PubMed:12740381, PubMed:14641107, PubMed:15470020, PubMed:22130794). Interacts with CCND3, CCNE1, DDX5, CASP3. 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 (By similarity). Interacts with DPY30; mediating AKAP8 association with at least the MLL4/WBP7 HMT complex (PubMed:23995757). Interacts with HDAC3; increased during mitosis (PubMed:16980585). 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 (PubMed:26880274).By similarity1 Publication12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CASP3P425745EBI-1237481,EBI-524064
HDAC3O1537910EBI-1237481,EBI-607682
MCM2P497367EBI-1237481,EBI-374819
PRKAR2AP138613EBI-1237481,EBI-2556122
RPS6KA1Q154185EBI-1237481,EBI-963034

GO - Molecular functioni

  • histone deacetylase binding Source: UniProtKB
  • protein kinase A regulatory subunit binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115561. 49 interactors.
DIPiDIP-38194N.
IntActiO43823. 39 interactors.
MINTiMINT-2796393.
STRINGi9606.ENSP00000269701.

Structurei

3D structure databases

ProteinModelPortaliO43823.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 210Interaction with DPY301 PublicationAdd BLAST210
Regioni1 – 195Interaction with MCM21 PublicationAdd BLAST195
Regioni109 – 201Interaction with DDX5By similarityAdd BLAST93
Regioni387 – 450Involved in chromatin-binding1 PublicationAdd BLAST64
Regioni525 – 569Involved in condensin complex recruitment1 PublicationAdd BLAST45
Regioni572 – 589RII-bindingBy similarityAdd BLAST18
Regioni576 – 593Required for interaction with MYCBPBy similarityAdd BLAST18

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi289 – 306Bipartite nuclear localization signalBy similarity1 PublicationAdd BLAST18

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi107 – 118Poly-GlyAdd BLAST12

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 fingeri392 – 414C2H2 AKAP95-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri481 – 504C2H2 AKAP95-type 2PROSITE-ProRule annotationAdd BLAST24

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IFNG. Eukaryota.
ENOG410YE5A. LUCA.
GeneTreeiENSGT00530000063777.
HOGENOMiHOG000033876.
HOVERGENiHBG053198.
InParanoidiO43823.
KOiK16525.
OMAiGCGRSQT.
OrthoDBiEOG091G0836.
PhylomeDBiO43823.
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.

O43823-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDQGYGGYGA WSAGPANTQG AYGTGVASWQ GYENYNYYGA QNTSVTTGAT
60 70 80 90 100
YSYGPASWEA AKANDGGLAA GAPAMHMASY GPEPCTDNSD SLIAKINQRL
110 120 130 140 150
DMMSKEGGRG GSGGGGEGIQ DRESSFRFQP FESYDSRPCL PEHNPYRPSY
160 170 180 190 200
SYDYEFDLGS DRNGSFGGQY SECRDPARER GSLDGFMRGR GQGRFQDRSN
210 220 230 240 250
PGTFMRSDPF VPPAASSEPL STPWNELNYV GGRGLGGPSP SRPPPSLFSQ
260 270 280 290 300
SMAPDYGVMG MQGAGGYDST MPYGCGRSQP RMRDRDRPKR RGFDRFGPDG
310 320 330 340 350
TGRKRKQFQL YEEPDTKLAR VDSEGDFSEN DDAAGDFRSG DEEFKGEDEL
360 370 380 390 400
CDSGRQRGEK EDEDEDVKKR REKQRRRDRT RDRAADRIQF ACSVCKFRSF
410 420 430 440 450
DDEEIQKHLQ SKFHKETLRF ISTKLPDKTV EFLQEYIVNR NKKIEKRRQE
460 470 480 490 500
LMEKETAKPK PDPFKGIGQE HFFKKIEAAH CLACDMLIPA QPQLLQRHLH
510 520 530 540 550
SVDHNHNRRL AAEQFKKTSL HVAKSVLNNR HIVKMLEKYL KGEDPFTSET
560 570 580 590 600
VDPEMEGDDN LGGEDKKETP EEVAADVLAE VITAAVRAVD GEGAPAPESS
610 620 630 640 650
GEPAEDEGPT DTAEAGSDPQ AEQLLEEQVP CGTAHEKGVP KARSEAAEAG
660 670 680 690
NGAETMAAEA ESAQTRVAPA PAAADAEVEQ TDAESKDAVP TE
Length:692
Mass (Da):76,108
Last modified:June 1, 1998 - v1
Checksum:iCBCD5F014FD94B66
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036534664Q → H in a breast cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y11997 mRNA. Translation: CAA72722.1.
AC005785 Genomic DNA. Translation: AAC62838.1.
CCDSiCCDS12329.1.
PIRiT13161.
RefSeqiNP_005849.1. NM_005858.3.
UniGeneiHs.594496.

Genome annotation databases

EnsembliENST00000269701; ENSP00000269701; ENSG00000105127.
GeneIDi10270.
KEGGihsa:10270.
UCSCiuc002nav.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y11997 mRNA. Translation: CAA72722.1.
AC005785 Genomic DNA. Translation: AAC62838.1.
CCDSiCCDS12329.1.
PIRiT13161.
RefSeqiNP_005849.1. NM_005858.3.
UniGeneiHs.594496.

3D structure databases

ProteinModelPortaliO43823.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115561. 49 interactors.
DIPiDIP-38194N.
IntActiO43823. 39 interactors.
MINTiMINT-2796393.
STRINGi9606.ENSP00000269701.

PTM databases

iPTMnetiO43823.
PhosphoSitePlusiO43823.
SwissPalmiO43823.

Polymorphism and mutation databases

BioMutaiAKAP8.

Proteomic databases

EPDiO43823.
MaxQBiO43823.
PaxDbiO43823.
PeptideAtlasiO43823.
PRIDEiO43823.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269701; ENSP00000269701; ENSG00000105127.
GeneIDi10270.
KEGGihsa:10270.
UCSCiuc002nav.4. human.

Organism-specific databases

CTDi10270.
GeneCardsiAKAP8.
HGNCiHGNC:378. AKAP8.
HPAiHPA004776.
MIMi604692. gene.
neXtProtiNX_O43823.
OpenTargetsiENSG00000105127.
PharmGKBiPA24672.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFNG. Eukaryota.
ENOG410YE5A. LUCA.
GeneTreeiENSGT00530000063777.
HOGENOMiHOG000033876.
HOVERGENiHBG053198.
InParanoidiO43823.
KOiK16525.
OMAiGCGRSQT.
OrthoDBiEOG091G0836.
PhylomeDBiO43823.
TreeFamiTF105407.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000105127-MONOMER.

Miscellaneous databases

ChiTaRSiAKAP8. human.
GeneWikiiAKAP8.
GenomeRNAii10270.
PROiO43823.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105127.
CleanExiHS_AKAP8.
ExpressionAtlasiO43823. baseline and differential.
GenevisibleiO43823. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: O43823
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: November 30, 2016
This is version 152 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.