P24588 (AKAP5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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
H21
cAMP-dependent protein kinase regulatory subunit II high affinity-binding protein

Gene names

Name:	AKAP5
Synonyms:	AKAP79

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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. Part of a complex containing AKAP5, ADCY5, ADCY6 AND PDE4C By similarity. Interacts with ADCY8, and enhances its phosphorylation at lipid rafts. Ref.7
Subcellular location	Membrane; Lipid-anchor. Note: Associates with lipid rafts. Ref.7
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. The N-terminal region, which is highly basic, is required for interaction with calmodulin.
Post-translational modification	Palmitoylation at Cys-36 and Cys-129 plays a key role in targeting to lipid rafts. Ref.7
Sequence similarities	Contains 1 AKAP domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Ligand	Calmodulin-binding
PTM	Lipoprotein Palmitate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	energy reserve metabolic process Traceable author statement. Source: Reactome positive regulation of cAMP biosynthetic process Inferred from mutant phenotype PubMed 17081159. Source: UniProtKB positive regulation of protein kinase A signaling cascade Inferred from mutant phenotype PubMed 17081159. Source: UniProtKB protein targeting Inferred from electronic annotation. Source: InterPro regulation of insulin secretion Traceable author statement. Source: Reactome signal transduction Non-traceable author statement Ref.1. Source: ProtInc small molecule metabolic process Traceable author statement. Source: Reactome synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome
Molecular_function	protein kinase A binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
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

Amino acid modifications

Lipidation

36

1

S-palmitoyl cysteine Ref.7

Lipidation

129

1

S-palmitoyl cysteine Ref.7

Natural variations

Natural variant

100

1

P → L.
Corresponds to variant rs2230491 [ dbSNP | Ensembl ].

VAR_056732

Natural variant

203

1

T → I. Ref.1 Ref.2 Ref.4 Ref.5
Corresponds to variant rs1256149 [ dbSNP | Ensembl ].

VAR_060735

Natural variant

314

1

E → K.
Corresponds to variant rs34433837 [ dbSNP | Ensembl ].

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 no nucleotide entry Ref.6

Secondary structure

1

.

.

.

427

Helix Strand Turn

Details...

Beta strand

339 – 344

6

Sequences

	Sequence		Length	Mass (Da)
	P24588 [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS, VARIANT ILE-203. Tissue: Thyroid.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-203. Tissue: Spleen.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-203.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-203.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 332-427. Tissue: Kidney.
[7]	"Palmitoylation targets AKAP79 protein to lipid rafts and promotes its regulation of calcium-sensitive adenylyl cyclase type 8." Delint-Ramirez I., Willoughby D., Hammond G.V., Ayling L.J., Cooper D.M. J. Biol. Chem. 286:32962-32975(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PALMITOYLATION AT CYS-36 AND CYS-129, INTERACTION WITH ADCY8, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M90359 mRNA. Translation: AAA58363.1.
AK315336 mRNA. Translation: BAG37736.1.
AL122035 Genomic DNA. No translation available.
CH471061 Genomic DNA. Translation: EAW80862.1.
BC131516 mRNA. Translation: AAI31517.1.

IPI

IPI00307794.

PIR

A43453.

RefSeq

NP_004848.3. NM_004857.3.

UniGene

Hs.656683.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2H9R	NMR	-	C	391-412	[»]
3LL8	X-ray	2.00	E	336-346	[»]

ProteinModelPortal

P24588.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-186N.

IntAct

P24588. 4 interactions.

MINT

MINT-1733931.

STRING

9606.ENSP00000315615.

PTM databases

PhosphoSite

P24588.

Polymorphism databases

DMDM

281185503.

Proteomic databases

PaxDb

P24588.

PRIDE

P24588.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000320636; ENSP00000315615; ENSG00000179841.
ENST00000394718; ENSP00000378207; ENSG00000179841.

GeneID

9495.

KEGG

hsa:9495.

UCSC

uc001xhd.4. human.

Organism-specific databases

CTD

9495.

GeneCards

GC14P064932.

H-InvDB

HIX0037749.

HGNC

HGNC:375. AKAP5.

HPA

CAB004308.

MIM

604688. gene.

neXtProt

NX_P24588.

PharmGKB

PA24669.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG25796.

HOGENOM

HOG000168350.

HOVERGEN

HBG050479.

InParanoid

P24588.

KO

K16522.

OMA

LVNEMAS.

PhylomeDB

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_111217. Metabolism.
REACT_13685. Neuronal System.

Gene expression databases

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

EvolutionaryTrace

P24588.

GenomeRNAi

9495.

NextBio

35572.

SOURCE

Search...

Entry information

Entry name

AKAP5_HUMAN

Accession

Primary (citable) accession number: P24588
Secondary accession number(s): A2RRB8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	December 15, 2009
Last modified:	May 1, 2013
This is version 119 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.