Reviewed, UniProtKB/Swiss-Prot P24588 (AKAP5_HUMAN)

Names and origin

Protein names

Recommended name:
A-kinase anchor protein 5
Short name=AKAP-5

Alternative name(s):
A-kinase anchor protein 79 kDa
Short name=AKAP 79
cAMP-dependent protein kinase regulatory subunit II high affinity-binding protein
H21

Gene names

Name:	AKAP5
Synonyms:	AKAP79

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	427 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May anchor the PKA protein to cytoskeletal and/or organelle-associated proteins, targeting the signal carried by cAMP to specific intracellular effectors. Association with to the beta2-adrenergic receptor (beta2-AR) not only regulates beta2-AR signaling pathway, but also the activation by PKA by switching off the beta2-AR signaling cascade.
Subunit structure	Binding protein for dimer of the RII-beta regulatory subunit of cAMP-dependent protein kinase (PKA) and also for the protein kinase C (PKC) and the phosphatase calcineurin (PP2B). Each enzyme is inhibited when bound to the anchoring protein. Also binds the beta2-adrenergic receptor.
Subcellular location	Membrane. Note: Associated with particulate fractions.
Tissue specificity	Predominantly in the cerebral cortex and the postsynaptic densities of the forebrain, and to a lesser extent in adrenal medulla, lung and anterior pituitary.
Domain	RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer.
Miscellaneous	The N-terminal region, which is highly basic, is required for interaction with calmodulin.
Sequence similarities	Contains 1 AKAP domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Ligand	Calmodulin-binding
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	positive regulation of cAMP biosynthetic process Inferred from mutant phenotype. Source: UniProtKB positive regulation of protein kinase A signaling cascade Inferred from mutant phenotype. Source: UniProtKB protein targeting Inferred from electronic annotation. Source: InterPro signal transduction Ref.1 Non-traceable author statement. Source: ProtInc synaptic transmission Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytosol Inferred from Experiment. Source: Reactome plasma membrane Ref.1 Inferred from Experiment. Source: Reactome
Molecular function	adenylate cyclase binding Inferred from physical interaction. Source: UniProtKB calmodulin binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase A binding Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
KCNJ2	P63252	1	EBI-703640,EBI-703457
Kcnj2	P35561	2	EBI-703640,EBI-703793	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 427

427

A-kinase anchor protein 5

PRO_0000064529

Regions

Domain

73 – 103

31

AKAP

Region

1 – 170

170

Essential to the intracellular anchoring function By similarity

Region

392 – 405

14

PKA-RII subunit binding domain

Natural variations

Natural variant

100

1

P → L: dbSNP rs2230491.

VAR_056732

Natural variant

203

1

T → I: dbSNP rs1256149. Ref.1

VAR_060735

Natural variant

314

1

E → K: dbSNP rs34433837.

VAR_056733

Experimental info

Mutagenesis

392

1

L → P: Prevents or diminishes RII binding.

Mutagenesis

396

1

A → P: Prevents or diminishes RII binding.

Mutagenesis

400

1

V → P: Prevents or diminishes RII binding.

Mutagenesis

405

1

Q → P: Prevents or diminishes RII binding.

Mutagenesis

408

1

I → P: Prevents or diminishes RII binding.

Sequence conflict

188

1

R → Q in AAA58363. Ref.1

Sequence conflict

407

1

S → Y Ref.3

Secondary structure

1

.

.

.

.

427

Helix Strand Turn

Details...

Helix

393 – 408

16

Turn

409 – 411

3

Sequences

	Sequence		Length	Mass (Da)
	P24588-1 [UniParc]. Last modified December 15, 2009. Version 3. Checksum: D2A86298EAF1BE32	FASTA	427	47,088
	10 20 30 40 50 60 METTISEIHV ENKDEKRSAE GSPGAERQKE KASMLCFKRR KKAAKALKPK AGSEAADVAR 70 80 90 100 110 120 KCPQEAGASD QPEPTRGAWA SLKRLVTRRK RSESSKQQKP LEGEMQPAIN AEDADLSKKK 130 140 150 160 170 180 AKSRLKIPCI KFPRGPKRSN HSKIIEDSDC SIKVQEEAEI LDIQTQTPLN DQATKAKSTQ 190 200 210 220 230 240 DLSEGISRKD GDEVCESNVS NSTTSGEKVI SVELGLDNGH SAIQTGTLIL EEIETIKEKQ 250 260 270 280 290 300 DVQPQQASPL ETSETDHQQP VLSDVPPLPA IPDQQIVEEA SNSTLESAPN GKDYESTEIV 310 320 330 340 350 360 AEETKPKDTE LSQESDFKEN GITEEKSKSE ESKRMEPIAI IITDTEISEF DVTKSKNVPK 370 380 390 400 410 420 QFLISAENEQ VGVFANDNGF EDRTSEQYET LLIETASSLV KNAIQLSIEQ LVNEMASDDN KINNLLQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Localization of the cAMP-dependent protein kinase to the postsynaptic densities by A-kinase anchoring proteins. Characterization of AKAP 79." Carr D.W., Stofko-Hahn R.E., Fraser I.D.C., Cone R.D., Scott J.D. J. Biol. Chem. 267:16816-16823(1992) [PubMed: 1512224] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS, VARIANT ILE-203. Tissue: Thyroid.
[2]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed: 12508121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Cloning and expression of an intron-less gene for AKAP 75, an anchor protein for the regulatory subunit of cAMP-dependent protein kinase II beta." Hirsch A.H., Glantz S.B., Li Y., You Y., Rubin C.S. J. Biol. Chem. 267:2131-2134(1992) [PubMed: 1733921] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 332-427. Tissue: Kidney.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M90359 mRNA. Translation: AAA58363.1.
AL122035 Genomic DNA. No translation available.

IPI

IPI00307794.

PIR

A43453.

RefSeq

NP_004848.3.

UniGene

Hs.656683

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2H9R	NMR	-	C	391-412	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-186N.

IntAct

P24588. 2 interactions.

STRING

P24588.

Genome annotation databases

Ensembl

ENST00000320636; ENSP00000315615; ENSG00000179841; Homo sapiens. [Genome view]
ENST00000430028; ENSP00000401880; ENSG00000179841; Homo sapiens. [Genome view]

GeneID

9495.

KEGG

hsa:9495.

Organism-specific databases

CTD

9495.

GeneCards

GC14P064003.

H-InvDB

HIX0037749.

HGNC

HGNC:375. AKAP5.

HPA

CAB004308.

MIM

604688. gene.

PharmGKB

PA24669.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG125229.

HOVERGEN

HBG050479.

InParanoid

P24588.

Enzyme and pathway databases

Pathway_Interaction_DB

tcrcalciumpathway. Calcium signaling in the CD4+ TCR pathway.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.

Reactome

REACT_13685. Synaptic Transmission.
REACT_15380. Diabetes pathways.

Gene expression databases

ArrayExpress

P24588.

Bgee

P24588.

CleanEx

HS_AKAP5.

Genevestigator

P24588.

GermOnline

ENSG00000179841. Homo sapiens.

Family and domain databases

InterPro

IPR001573. Pkinase-A_anch_WSK-motif.
[Graphical view]

Pfam

PF03832. WSK. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

Search...

Entry information

Entry name

AKAP5_HUMAN

Accession

Primary (citable) accession number: P24588

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	December 15, 2009
Last modified:	March 2, 2010
This is version 90 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.