AKAP13 (A-kinase anchoring protein 13)

Gene

• Entrez ID: 11214
• Gene name: A-kinase anchoring protein 13
• Gene symbol: AKAP13
• Synonyms: AKAP-13, AKAP-Lbc, ARHGEF13, BRX, HA-3, Ht31, LBC, PRKA13, PROTO-LB, PROTO-LBC, c-lbc, p47
• Chromosome: 15
• Chromosome location: 15q25.3
• Summary: The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms containing c-terminal dbl oncogene homology (DH) and pleckstrin homology (PH) domains. The DH domain is associated with guanine nucleotide exchange activation for the Rho/Rac family of small GTP binding proteins, resulting in the conversion of the inactive GTPase to the active form capable of transducing signals. The PH domain has multiple functions. Therefore, these isoforms function as scaffolding proteins to coordinate a Rho signaling pathway, function as protein kinase A-anchoring proteins and, in addition, enhance ligand-dependent activity of estrogen receptors alpha and beta. [provided by RefSeq, Jul 2012]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017303	hsa-miR-335-5p	Microarray	18185580
MIRT038038	hsa-miR-423-5p	CLASH	23622248
MIRT041492	hsa-miR-193b-3p	CLASH	23622248
MIRT042150	hsa-miR-484	CLASH	23622248
MIRT045632	hsa-miR-149-5p	CLASH	23622248
MIRT051060	hsa-miR-16-5p	CLASH	23622248
MIRT662349	hsa-miR-6749-3p	HITS-CLIP	23824327
MIRT662349	hsa-miR-6749-3p	HITS-CLIP	19536157
MIRT662350	hsa-miR-6792-3p	HITS-CLIP	23824327
MIRT662350	hsa-miR-6792-3p	HITS-CLIP	19536157
MIRT662351	hsa-miR-4691-5p	HITS-CLIP	23824327
MIRT662351	hsa-miR-4691-5p	HITS-CLIP	19536157
MIRT662352	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT662352	hsa-miR-211-5p	HITS-CLIP	19536157
MIRT662353	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT662353	hsa-miR-204-5p	HITS-CLIP	19536157
MIRT662354	hsa-miR-8074	HITS-CLIP	23824327
MIRT662354	hsa-miR-8074	HITS-CLIP	19536157
MIRT662355	hsa-miR-6778-3p	HITS-CLIP	23824327
MIRT662355	hsa-miR-6778-3p	HITS-CLIP	19536157
MIRT662356	hsa-miR-4287	HITS-CLIP	23824327
MIRT662356	hsa-miR-4287	HITS-CLIP	19536157
MIRT662357	hsa-miR-4685-3p	HITS-CLIP	23824327
MIRT662357	hsa-miR-4685-3p	HITS-CLIP	19536157
MIRT662358	hsa-miR-1281	HITS-CLIP	23824327
MIRT662358	hsa-miR-1281	HITS-CLIP	19536157
MIRT662359	hsa-miR-3667-3p	HITS-CLIP	23824327
MIRT662360	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT662360	hsa-miR-6832-3p	HITS-CLIP	19536157
MIRT662361	hsa-miR-183-5p	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004691	Function	CAMP-dependent protein kinase activity	IEA
GO:0005078	Function	MAP-kinase scaffold activity	IBA	21873635
GO:0005078	Function	MAP-kinase scaffold activity	IDA	21224381
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IDA	11546812, 25186459
GO:0005515	Function	Protein binding	IPI	9627117, 15161933, 16301118, 21224381, 28514442
GO:0005634	Component	Nucleus	IEA
GO:0005829	Component	Cytosol	IDA	11546812
GO:0005829	Component	Cytosol	TAS
GO:0005938	Component	Cell cortex	IDA	11546812
GO:0006468	Process	Protein phosphorylation	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IDA	11546812
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007507	Process	Heart development	ISS
GO:0015629	Component	Actin cytoskeleton	IBA	21873635
GO:0016020	Component	Membrane	HDA	19946888
GO:0030864	Component	Cortical actin cytoskeleton	IDA	11546812
GO:0031267	Function	Small GTPase binding	IPI	25186459
GO:0035023	Process	Regulation of Rho protein signal transduction	IBA	21873635
GO:0035025	Process	Positive regulation of Rho protein signal transduction	IDA	11546812
GO:0035025	Process	Positive regulation of Rho protein signal transduction	IMP	21224381
GO:0043065	Process	Positive regulation of apoptotic process	TAS
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IBA	21873635
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP	23090968
GO:0043406	Process	Positive regulation of MAP kinase activity	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:0051018	Function	Protein kinase A binding	IDA	11546812
GO:0051056	Process	Regulation of small GTPase mediated signal transduction	TAS
GO:0051168	Process	Nuclear export	IEA
GO:0055007	Process	Cardiac muscle cell differentiation	ISS
GO:0060090	Function	Molecular adaptor activity	IDA	23090968
GO:0060297	Process	Regulation of sarcomere organization	ISS
GO:0060348	Process	Bone development	ISS
GO:0061049	Process	Cell growth involved in cardiac muscle cell development	IEA
GO:0071875	Process	Adrenergic receptor signaling pathway	IBA	21873635
GO:0071875	Process	Adrenergic receptor signaling pathway	IMP	21224381, 23090968
GO:0086023	Process	Adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process	ISS

Other IDs

• MIM: 604686
• HGNC: 371
• e!Ensembl: ENSG00000170776

Protein

• UniProt ID: Q12802
• Protein name: A-kinase anchor protein 13 (AKAP-13) (AKAP-Lbc) (Breast cancer nuclear receptor-binding auxiliary protein) (Guanine nucleotide exchange factor Lbc) (Human thyroid-anchoring protein 31) (Lymphoid blast crisis oncogene) (LBC oncogene) (Non-oncogenic Rho GTPase-specific GTP exchange factor) (Protein kinase A-anchoring protein 13) (PRKA13) (p47)
• Protein function: Scaffold protein that plays an important role in assembling signaling complexes downstream of several types of G protein-coupled receptors. Activates RHOA in response to signaling via G protein-coupled receptors via its function as Rho guanine nucleotide exchange factor (PubMed:11546812, PubMed:15229649, PubMed:23090968, PubMed:25186459, PubMed:24993829). May also activate other Rho family members (PubMed:11546812). Part of a kinase signaling complex that links ADRA1A and ADRA1B adrenergic receptor signaling to the activation of downstream p38 MAP kinases, such as MAPK11 and MAPK14 (PubMed:17537920, PubMed:23716597, PubMed:21224381). Part of a signaling complex that links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade that mediates responses to lysophosphatidic acid (LPA), a signaling molecule that activates G-protein coupled receptors and potentiates transcriptional activation of the glucocorticoid receptor NR3C1 (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-dependent gene expression in response to lysophosphatidic acid (LPA) (By similarity). Part of a signaling pathway that activates MAPK11 and/or MAPK14 and leads to increased transcription activation of the estrogen receptors ESR1 and ESR2 (PubMed:9627117, PubMed:11579095). Part of a signaling cascade that links cAMP and EGFR signaling to BRAF signaling and to PKA-mediated phosphorylation of KSR1, leading to the activation of downstream MAP kinases, such as MAPK1 or MAPK3 (PubMed:21102438). Functions as scaffold protein that anchors cAMP-dependent protein kinase (PKA) and PRKD1. This promotes activation of PRKD1, leading to increased phosphorylation of HDAC5 and ultimately cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for normal embryonic heart development, and in particular for normal sarcomere formation in the developing cardiomyocytes (By similarity). Plays a role in cardiomyocyte growth and cardiac hypertrophy in response to activation of the beta-adrenergic receptor by phenylephrine or isoproterenol (PubMed:17537920, PubMed:23090968). Required for normal adaptive cardiac hypertrophy in response to pressure overload (PubMed:23716597). Plays a role in osteogenesis (By similarity).
• PDB: 2DRN, 2LG1, 4D0N, 4D0O, 6BCA
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF10522	RII_binding_1	1246 → 1264	RII binding domain	Motif
  PF00621	RhoGEF	1998 → 2189	RhoGEF domain	Domain
  PF00169	PH	2216 → 2333	PH domain	Domain

• Sequence:

  MKLNPQQAPLYGDCVVTVLLAEEDKAEDDVVFYLVFLGSTLRHCTSTRKVSSDTLETIAP
  GHDCCETVKVQLCASKEGLPVFVVAEEDFHFVQDEAYDAAQFLATSAGNQQALNFTRFLD
  QSGPPSGDVNSLDKKLVLAFRHLKLPTEWNVLGTDQSLHDAGPRETLMHFAVRLGLLRLT
  WFLLQKPGGRGALSIHNQEGATPVSLALERGYHKLHQLLTEENAGEPDSWSSLSYEIPYG
  DCSVRHHRELDIYTLTSESDSHHEHPFPGDGCTGPIFKLMNIQQQLMKTNLKQMDSLMPL
  MMTAQDPSSAPETDGQFLPCAPEPTDPQRLSSSEETESTQCCPGSPVAQTESPCDLSSIV
  EEENTDRSCRKKNKGVERKGEEVEPAPIVDSGTVSDQDSCLQSLPDCGVKGTEGLSSCGN
  RNEETGTKSSGMPTDQESLSSGDAVLQRDLVMEPGTAQYSSGGELGGISTTNVSTPDTAG
  EMEHGLMNPDATVWKNVLQGGESTKERFENSNIGTAGASDVHVTSKPVDKISVPNCAPAA
  SSLDGNKPAESSLAFSNEETSTEKTAETETSRSREESADAPVDQNSVVIPAAAKDKISDG
  LEPYTLLAAGIGEAMSPSDLALLGLEEDVMPHQNSETNSSHAQSQKGKSSPICSTTGDDK
  LCADSACQQNTVTSSGDLVAKLCDNIVSESESTTARQPSSQDPPDASHCEDPQAHTVTSD
  PVRDTQERADFCPFKVVDNKGQRKDVKLDKPLTNMLEVVSHPHPVVPKMEKELVPDQAVI
  SDSTFSLANSPGSESVTKDDALSFVPSQKEKGTATPELHTATDYRDGPDGNSNEPDTRPL
  EDRAVGLSTSSTAAELQHGMGNTSLTGLGGEHEGPAPPAIPEALNIKGNTDSSLQSVGKA
  TLALDSVLTEEGKLLVVSESSAAQEQDKDKAVTCSSIKENALSSGTLQEEQRTPPPGQDT
  QQFHEKSISADCAKDKALQLSNSPGASSAFLKAETEHNKEVAPQVSLLTQGGAAQSLVPP
  GASLATESRQEALGAEHNSSALLPCLLPDGSDGSDALNCSQPSPLDVGVKNTQSQGKTSA
  CEVSGDVTVDVTGVNALQGMAEPRRENISHNTQDILIPNVLLSQEKNAVLGLPVALQDKA
  VTDPQGVGTPEMIPLDWEKGKLEGADHSCTMGDAEEAQIDDEAHPVLLQPVAKELPTDME
  LSAHDDGAPAGVREVMRAPPSGRERSTPSLPCMVSAQDAPLPKGADLIEEAASRIVDAVI
  EQVKAAGALLTEGEACHMSLSSPELGPLTKGLESAFTEKVSTFPPGESLPMGSTPEEATG
  SLAGCFAGREEPEKIILPVQGPEPAAEMPDVKAEDEVDFRASSISEEVAVGSIAATLKMK
  QGPMTQAINRENWCTIEPCPDAASLLASKQSPECENFLDVGLGRECTSKQGVLKRESGSD
  SDLFHSPSDDMDSIIFPKPEEEHLACDITGSSSSTDDTASLDRHSSHGSDVSLSQILKPN
  RSRDRQSLDGFYSHGMGAEGRESESEPADPGDVEEEEMDSITEVPANCSVLRSSMRSLSP
  FRRHSWGPGKNAASDAEMNHRSSMRVLGDVVRRPPIHRRSFSLEGLTGGAGVGNKPSSSL
  EVSSANAEELRHPFSGEERVDSLVSLSEEDLESDQREHRMFDQQICHRSKQQGFNYCTSA
  ISSPLTKSISLMTISHPGLDNSRPFHSTFHNTSANLTESITEENYNFLPHSPSKKDSEWK
  SGTKVSRTFSYIKNKMSSSKKSKEKEKEKDKIKEKEKDSKDKEKDKKTVNGHTFSSIPVV
  GPISCSQCMKPFTNKDAYTCANCSAFVHKGCRESLASCAKVKMKQPKGSLQAHDTSSLPT
  VIMRNKPSQPKERPRSAVLLVDETATTPIFANRRSQQSVSLSKSVSIQNITGVGNDENMS
  NTWKFLSHSTDSLNKISKVNESTESLTDEGVGTDMNEGQLLGDFEIESKQLEAESWSRII
  DSKFLKQQKKDVVKRQEVIYELMQTEFHHVRTLKIMSGVYSQGMMADLLFEQQMVEKLFP
  CLDELISIHSQFFQRILERKKESLVDKSEKNFLIKRIGDVLVNQFSGENAERLKKTYGKF
  CGQHNQSVNYFKDLYAKDKRFQAFVKKKMSSSVVRRLGIPECILLVTQRITKYPVLFQRI
  LQCTKDNEVEQEDLAQSLSLVKDVIGAVDSKVASYEKKVRLNEIYTKTDSKSIMRMKSGQ
  MFAKEDLKRKKLVRDGSVFLKNAAGRLKEVQAVLLTDILVFLQEKDQKYIFASLDQKSTV
  ISLKKLIVREVAHEEKGLFLISMGMTDPEMVEVHASSKEERNSWIQIIQDTINTLNRDED
  EGIPSENEEEKKMLDTRARELKEQLHQKDQKILLLLEEKEMIFRDMAECSTPLPEDCSPT
  HSPRVLFRSNTEEALKGGPLMKSAINEVEILQGLVSGNLGGTLGPTVSSPIEQDVVGPVS
  LPRRAETFGGFDSHQMNASKGGEKEEGDDGQDLRRTESDSGLKKGGNANLVFMLKRNSEQ
  VVQSVVHLYELLSALQGVVLQQDSYIEDQKLVLSERALTRSLSRPSSLIEQEKQRSLEKQ
  RQDLANLQKQQAQYLEEKRRREREWEARERELREREALLAQREEEVQQGQQDLEKEREEL
  QQKKGTYQYDLERLRAAQKQLEREQEQLRREAERLSQRQTERDLCQVSHPHTKLMRIPSF
  FPSPEEPPSPSAPSIAKSGSLDSELSVSPKRNSISRTHKDKGPFHILSSTSQTNKGPEGQ
  SQAPASTSASTRLFGLTKPKEKKEKKKKNKTSRSQPGDGPASEVSAEGEEIFC

• Sequence length: 2813

Pathways

KEGG:

Parathyroid hormone synthesis, secretion and action
Human cytomegalovirus infection

Reactome:

NRAGE signals death through JNK
Rho GTPase cycle
G alpha (12/13) signalling events

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Papillary renal carcinoma	Papillary Renal Cell Carcinoma	rs5030823, rs2137087134, rs121913668, rs121913669, rs121913670, rs121913671, rs121913673, rs121913243, rs786202724	22138691
Chromophobe carcinoma	Chromophobe Renal Cell Carcinoma	rs-1	22138691
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	29212778
Prostate cancer	Malignant neoplasm of prostate	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	28319090
Esophagus neoplasm	Esophageal Neoplasms, Malignant neoplasm of esophagus	rs28934578, rs121918714, rs1567556006, rs1575166666	17068819
Renal carcinoma	Renal Cell Carcinoma, Conventional (Clear Cell) Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma, Collecting Duct Carcinoma of the Kidney	rs121913668, rs121913670, rs121913243, rs786202724	22138691

Unknown
Disease name	Disease term	dbSNP ID	References
Lung diseases	Lung Diseases, Interstitial		23583980
Prostatic neoplasms	Prostatic Neoplasms		28319090