O43572 (AKA10_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
A-kinase anchor protein 10, mitochondrial
Short name=AKAP-10

Alternative name(s):
Dual specificity A kinase-anchoring protein 2
Short name=D-AKAP-2
Protein kinase A-anchoring protein 10
Short name=PRKA10

Gene names

Name:

AKAP10

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	662 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Differentially targeted protein that binds to type I and II regulatory subunits of protein kinase A and anchors them to the mitochondria or the plasma membrane. Although the physiological relevance between PKA and AKAPS with mitochondria is not fully understood, one idea is that BAD, a proapoptotic member, is phosphorylated and inactivated by mitochondria-anchored PKA. It cannot be excluded too that it may facilitate PKA as well as G protein signal transduction, by acting as an adapter for assembling multiprotein complexes. With its RGS domain, it could lead to the interaction to G-alpha proteins, providing a link between the signaling machinery and the downstream kinase By similarity.
Subcellular location	Mitochondrion. Membrane. Cytoplasm. Note: Predominantly mitochondrial but also membrane associated and cytoplasmic. Ref.1
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.
Involvement in disease	Genetic variations in AKAP10 are a cause of susceptibility to sudden cardiac death (SCD) [MIM:115080]. Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as chest pain and cardiac arrhythmias, particularly ventricular tachycardia, can lead to the loss of consciousness and cardiac arrest followed by biological death. Note=Increased susceptibility to sudden cardiac death may be conferred by AKAP10 variants that are associated with markers of low vagus nerve sensitivity, e.g., fast basal heart rate and low heart rate variability. Ref.7
Sequence similarities	Contains 2 RGS domains.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Repeat Transit peptide
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	blood coagulation Traceable author statement. Source: Reactome protein localization Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay. Source: HPA
Molecular function	signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 28

28

Mitochondrion Potential

Chain

29 – 662

634

A-kinase anchor protein 10, mitochondrial

PRO_0000030404

Regions

Domain

125 – 369

245

RGS 1

Domain

379 – 505

127

RGS 2

Region

634 – 647

14

PKA-RII subunit binding

Amino acid modifications

Modified residue

52

1

Phosphoserine Ref.6

Modified residue

187

1

Phosphoserine Ref.6

Natural variations

Natural variant

249

1

R → H.
Corresponds to variant rs2108978 [ dbSNP | Ensembl ].

VAR_024607

Natural variant

646

1

I → V Associated with increased basal heart rate and decreased heart rate variability. Ref.7
Corresponds to variant rs203462 [ dbSNP | Ensembl ].

VAR_024608

Experimental info

Sequence conflict

177

1

V → M in AAB92260. Ref.2

Sequence conflict

524

1

L → P in AAB92260. Ref.2

Secondary structure

1

.

.

.

662

Helix Strand Turn

Details...

Helix

629 – 653

25

Sequences

	Sequence		Length	Mass (Da)
	O43572 [UniParc]. Last modified July 19, 2005. Version 2. Checksum: B7A6D92CA2D3D794	FASTA	662	73,818
	10 20 30 40 50 60 MRGAGPSPRQ SPRTLRPDPG PAMSFFRRKV KGKEQEKTSD VKSIKASISV HSPQKSTKNH 70 80 90 100 110 120 ALLEAAGPSH VAINAISANM DSFSSSRTAT LKKQPSHMEA AHFGDLGRSC LDYQTQETKS 130 140 150 160 170 180 SLSKTLEQVL HDTIVLPYFI QFMELRRMEH LVKFWLEAES FHSTTWSRIR AHSLNTVKQS 190 200 210 220 230 240 SLAEPVSPSK KHETTASFLT DSLDKRLEDS GSAQLFMTHS EGIDLNNRTN STQNHLLLSQ 250 260 270 280 290 300 ECDSAHSLRL EMARAGTHQV SMETQESSST LTVASRNSPA SPLKELSGKL MKSIEQDAVN 310 320 330 340 350 360 TFTKYISPDA AKPIPITEAM RNDIIARICG EDGQVDPNCF VLAQSIVFSA MEQEHFSEFL 370 380 390 400 410 420 RSHHFCKYQI EVLTSGTVYL ADILFCESAL FYFSEYMEKE DAVNILQFWL AADNFQSQLA 430 440 450 460 470 480 AKKGQYDGQE AQNDAMILYD KYFSLQATHP LGFDDVVRLE IESNICREGG PLPNCFTTPL 490 500 510 520 530 540 RQAWTTMEKV FLPGFLSSNL YYKYLNDLIH SVRGDEFLGG NVSLTAPGSV GPPDESHPGS 550 560 570 580 590 600 SDSSASQSSV KKASIKILKN FDEAIIVDAA SLDPESLYQR TYAGKMTFGR VSDLGQFIRE 610 620 630 640 650 660 SEPEPDVRKS KGSMFSQAMK KWVQGNTDEA QEELAWKIAK MIVSDIMQQA QYDQPLEKST KL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and mitochondrial localization of full-length D-AKAP2, a protein kinase A anchoring protein." Wang L., Sunahara R.K., Krumins A., Perkins G., Crochiere M.L., Mackey M., Bell S., Ellisman M.H., Taylor S.S. Proc. Natl. Acad. Sci. U.S.A. 98:3220-3225(2001) [PubMed: 11248059] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION. Tissue: Brain.
[2]	"Homo sapiens protein kinase A anchoring protein with an RGS domain." Chatterjee T.K., Fisher R.A. Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[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].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[6]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52 AND SER-187, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"Gene-trapped mouse embryonic stem cell-derived cardiac myocytes and human genetics implicate AKAP10 in heart rhythm regulation." Tingley W.G., Pawlikowska L., Zaroff J.G., Kim T., Nguyen T., Young S.G., Vranizan K., Kwok P.Y., Whooley M.A., Conklin B.R. Proc. Natl. Acad. Sci. U.S.A. 104:8461-8466(2007) [PubMed: 17485678] [Abstract] Cited for: VARIANT VAL-646, INVOLVEMENT IN SUSCEPTIBILITY TO SCD.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF037439 mRNA. Translation: AAB92260.1.
AK312438 mRNA. Translation: BAG35347.1.
CH471212 Genomic DNA. Translation: EAW50913.1.
BC017055 mRNA. Translation: AAH17055.1.

IPI

IPI00306265.

RefSeq

NP_009133.2. NM_007202.2.

UniGene

Hs.642676.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IM4	X-ray	2.28	C	623-662	[»]

ProteinModelPortal

O43572.

SMR

O43572. Positions 373-507, 628-654.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48753N.

IntAct

O43572. 1 interaction.

MINT

MINT-1473023.

STRING

O43572.

PTM databases

PhosphoSite

O43572.

Proteomic databases

PRIDE

O43572.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000225737; ENSP00000225737; ENSG00000108599.

GeneID

11216.

KEGG

hsa:11216.

UCSC

uc002gwo.1. human.

Organism-specific databases

CTD

11216.

GeneCards

GC17M019749.

H-InvDB

HIX0017647.

HGNC

HGNC:368. AKAP10.

HPA

HPA028901.

MIM

115080. phenotype.
604694. gene.

neXtProt

NX_O43572.

PharmGKB

PA24662.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG11229.

GeneTree

ENSGT00390000015077.

HOGENOM

HBG446504.

HOVERGEN

HBG050469.

InParanoid

O43572.

OMA

QFIRESE.

OrthoDB

EOG4DJJVX.

PhylomeDB

O43572.

Enzyme and pathway databases

Reactome

REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

O43572.

Bgee

O43572.

CleanEx

HS_AKAP10.

Genevestigator

O43572.

GermOnline

ENSG00000108599. Homo sapiens.

Family and domain databases

InterPro

IPR000342. Regulat_G_prot_signal.
IPR016137. Regulat_G_prot_signal_superfam.
[Graphical view]

Pfam

PF00615. RGS. 2 hits.
[Graphical view]

SMART

SM00315. RGS. 2 hits.
[Graphical view]

SUPFAM

SSF48097. Regulat_G_prot_signal_superfam. 2 hits.

PROSITE

PS50132. RGS. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

42691.

SOURCE

Search...

Entry information

Entry name

AKA10_HUMAN

Accession

Primary (citable) accession number: O43572
Secondary accession number(s): B2R650, Q96AJ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	July 19, 2005
Last modified:	January 25, 2012
This is version 91 of the entry and version 2 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.