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Protein

A-kinase anchor protein 8

Gene

AKAP8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • NF-kappaB binding Source: Ensembl
  • protein kinase A regulatory subunit binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • zinc ion binding Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionDNA-binding
Biological processImmunity, Innate immunity, Protein transport, Transcription, Transcription regulation, Transport
LigandMetal-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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105127.8
HGNCiHGNC:378 AKAP8
MIMi604692 gene
neXtProtiNX_O43823

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

DisGeNETi10270
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
Cross-linki317Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei323PhosphoserineCombined sources1
Modified residuei328PhosphoserineCombined sources1
Modified residuei339PhosphoserineCombined sources1
Cross-linki567Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
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

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO43823
MaxQBiO43823
PaxDbiO43823
PeptideAtlasiO43823
PRIDEiO43823
ProteomicsDBi49189

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 Expressed in 223 organ(s), highest expression level in epithelium of mammary gland
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115561, 54 interactors
DIPiDIP-38194N
IntActiO43823, 56 interactors
MINTiO43823
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

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
OMAiWQGYENY
OrthoDBiEOG091G0836
PhylomeDBiO43823
TreeFamiTF105407

Family and domain databases

InterProiView protein in InterPro
IPR007071 AKAP95
IPR034736 ZF_C2H2_AKAP95
PANTHERiPTHR12190 PTHR12190, 1 hit
PfamiView protein in Pfam
PF04988 AKAP95, 1 hit
PROSITEiView protein in PROSITE
PS51799 ZF_C2H2_AKAP95, 2 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0QYL4M0QYL4_HUMAN
A-kinase anchor protein 8
AKAP8
178Annotation score:
M0QX51M0QX51_HUMAN
A-kinase anchor protein 8
AKAP8
133Annotation score:

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

Similar proteinsi

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, 54 interactors
DIPiDIP-38194N
IntActiO43823, 56 interactors
MINTiO43823
STRINGi9606.ENSP00000269701

PTM databases

iPTMnetiO43823
PhosphoSitePlusiO43823
SwissPalmiO43823

Polymorphism and mutation databases

BioMutaiAKAP8

Proteomic databases

EPDiO43823
MaxQBiO43823
PaxDbiO43823
PeptideAtlasiO43823
PRIDEiO43823
ProteomicsDBi49189

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi10270
DisGeNETi10270
EuPathDBiHostDB:ENSG00000105127.8
GeneCardsiAKAP8
HGNCiHGNC:378 AKAP8
HPAiHPA004776
MIMi604692 gene
neXtProtiNX_O43823
OpenTargetsiENSG00000105127
PharmGKBiPA24672
GenAtlasiSearch...

Phylogenomic databases

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

Miscellaneous databases

ChiTaRSiAKAP8 human
GeneWikiiAKAP8
GenomeRNAii10270
PROiPR:O43823
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105127 Expressed in 223 organ(s), highest expression level in epithelium of mammary gland
CleanExiHS_AKAP8
ExpressionAtlasiO43823 baseline and differential
GenevisibleiO43823 HS

Family and domain databases

InterProiView protein in InterPro
IPR007071 AKAP95
IPR034736 ZF_C2H2_AKAP95
PANTHERiPTHR12190 PTHR12190, 1 hit
PfamiView protein in Pfam
PF04988 AKAP95, 1 hit
PROSITEiView protein in PROSITE
PS51799 ZF_C2H2_AKAP95, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiAKAP8_HUMAN
AccessioniPrimary (citable) accession number: O43823
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: November 7, 2018
This is version 166 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
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