AKP13_MOUSE
ID AKP13_MOUSE Reviewed; 2776 AA.
AC E9Q394; Q3UEI5;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=A-kinase anchor protein 13;
DE Short=AKAP-13;
DE AltName: Full=AKAP-Lbc {ECO:0000303|PubMed:17537920};
GN Name=Akap13 {ECO:0000312|MGI:MGI:2676556};
GN Synonyms=Brx {ECO:0000303|PubMed:16469733};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|Proteomes:UP000000589};
RN [1] {ECO:0000312|Ensembl:ENSMUSP00000129784, ECO:0000312|Proteomes:UP000000589}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J {ECO:0000312|Ensembl:ENSMUSP00000129784,
RC ECO:0000312|Proteomes:UP000000589};
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 804-1696 (ISOFORM 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE28926.1};
RC TISSUE=Liver {ECO:0000312|EMBL:BAE28926.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=16469733; DOI=10.1074/jbc.m509339200;
RA Kino T., Souvatzoglou E., Charmandari E., Ichijo T., Driggers P.,
RA Mayers C., Alatsatianos A., Manoli I., Westphal H., Chrousos G.P.,
RA Segars J.H.;
RT "Rho family Guanine nucleotide exchange factor Brx couples extracellular
RT signals to the glucocorticoid signaling system.";
RL J. Biol. Chem. 281:9118-9126(2006).
RN [4]
RP FUNCTION, AND INDUCTION BY PHENYLEPHRINE.
RX PubMed=17537920; DOI=10.1073/pnas.0701099104;
RA Appert-Collin A., Cotecchia S., Nenniger-Tosato M., Pedrazzini T.,
RA Diviani D.;
RT "The A-kinase anchoring protein (AKAP)-Lbc-signaling complex mediates
RT alpha1 adrenergic receptor-induced cardiomyocyte hypertrophy.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:10140-10145(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1839 AND SER-2692, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-941; SER-1608; SER-1611;
RP SER-1613; SER-1839; SER-1892; SER-1895; SER-2361; SER-2527; SER-2530 AND
RP SER-2692, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH
RP MEF2C AND RXRB, AND TISSUE SPECIFICITY.
RX PubMed=20139090; DOI=10.1074/jbc.m110.106856;
RA Mayers C.M., Wadell J., McLean K., Venere M., Malik M., Shibata T.,
RA Driggers P.H., Kino T., Guo X.C., Koide H., Gorivodsky M., Grinberg A.,
RA Mukhopadhyay M., Abu-Asab M., Westphal H., Segars J.H.;
RT "The Rho guanine nucleotide exchange factor AKAP13 (BRX) is essential for
RT cardiac development in mice.";
RL J. Biol. Chem. 285:12344-12354(2010).
RN [9]
RP INTERACTION WITH KSR1; BRAF; PKA AND PRKAR2A.
RX PubMed=21102438; DOI=10.1038/ncb2130;
RA Smith F.D., Langeberg L.K., Cellurale C., Pawson T., Morrison D.K.,
RA Davis R.J., Scott J.D.;
RT "AKAP-Lbc enhances cyclic AMP control of the ERK1/2 cascade.";
RL Nat. Cell Biol. 12:1242-1249(2010).
RN [10]
RP INTERACTION WITH IKBKB.
RX PubMed=23090968; DOI=10.1128/mcb.00887-12;
RA del Vescovo C.D., Cotecchia S., Diviani D.;
RT "A-kinase-anchoring protein-Lbc anchors IkappaB kinase beta to support
RT interleukin-6-mediated cardiomyocyte hypertrophy.";
RL Mol. Cell. Biol. 33:14-27(2013).
RN [11]
RP FUNCTION, INTERACTION WITH PRKD1 AND PKA, AND DEVELOPMENTAL STAGE.
RX PubMed=23658642; DOI=10.1371/journal.pone.0062705;
RA Spindler M.J., Burmeister B.T., Huang Y., Hsiao E.C., Salomonis N.,
RA Scott M.J., Srivastava D., Carnegie G.K., Conklin B.R.;
RT "AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but
RT have an abnormal response to beta-adrenergic-induced cardiac hypertrophy.";
RL PLoS ONE 8:E62705-E62705(2013).
RN [12]
RP FUNCTION, AND INTERACTION WITH PRKD1 AND PKA.
RX PubMed=24161911; DOI=10.1016/j.yjmcc.2013.10.010;
RA Taglieri D.M., Johnson K.R., Burmeister B.T., Monasky M.M., Spindler M.J.,
RA DeSantiago J., Banach K., Conklin B.R., Carnegie G.K.;
RT "The C-terminus of the long AKAP13 isoform (AKAP-Lbc) is critical for
RT development of compensatory cardiac hypertrophy.";
RL J. Mol. Cell. Cardiol. 66:27-40(2014).
RN [13]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=25892096; DOI=10.1002/jbmr.2534;
RA Koide H., Holmbeck K., Lui J.C., Guo X.C., Driggers P., Chu T., Tatsuno I.,
RA Quaglieri C., Kino T., Baron J., Young M.F., Robey P.G., Segars J.H.;
RT "Mice deficient in AKAP13 (BRX) are osteoporotic and have impaired
RT osteogenesis.";
RL J. Bone Miner. Res. 30:1887-1895(2015).
CC -!- FUNCTION: Scaffold protein that plays an important role in assembling
CC signaling complexes downstream of several types of G protein-coupled
CC receptors. Activates RHOA in response to signaling via G protein-
CC coupled receptors via its function as Rho guanine nucleotide exchange
CC factor. May also activate other Rho family members (PubMed:23658642).
CC Part of a kinase signaling complex that links ADRA1A and ADRA1B
CC adrenergic receptor signaling to the activation of downstream p38 MAP
CC kinases, such as MAPK11 and MAPK14. Part of a signaling complex that
CC links ADRA1B signaling to the activation of RHOA and IKBKB/IKKB,
CC leading to increased NF-kappa-B transcriptional activity. Part of a
CC RHOA-dependent signaling cascade that mediates responses to
CC lysophosphatidic acid (LPA), a signaling molecule that activates G-
CC protein coupled receptors and potentiates transcriptional activation of
CC the glucocorticoid receptor NR3C1 (By similarity). Part of a signaling
CC cascade that stimulates MEF2C-dependent gene expression in response to
CC lysophosphatidic acid (LPA) (By similarity). Part of a signaling
CC pathway that activates MAPK11 and/or MAPK14 and leads to increased
CC transcription activation of the estrogen receptors ESR1 and ESR2. Part
CC of a signaling cascade that links cAMP and EGFR signaling to BRAF
CC signaling and to PKA-mediated phosphorylation of KSR1, leading to the
CC activation of downstream MAP kinases, such as MAPK1 or MAPK3 (By
CC similarity). Functions as scaffold protein that anchors cAMP-dependent
CC protein kinase (PKA) and PRKD1. This promotes activation of PRKD1,
CC leading to increased phosphorylation of HDAC5 and ultimately
CC cardiomyocyte hypertrophy (PubMed:24161911). Has no guanine nucleotide
CC exchange activity on CDC42, Ras or Rac (By similarity). Required for
CC normal embryonic heart development, and in particular for normal
CC sarcomere formation in the developing cardiomyocytes (PubMed:20139090).
CC Plays a role in cardiomyocyte growth and cardiac hypertrophy in
CC response to activation of the beta-adrenergic receptor by phenylephrine
CC or isoproterenol (PubMed:23658642, PubMed:24161911). Required for
CC normal adaptive cardiac hypertrophy in response to pressure overload
CC (PubMed:17537920, PubMed:24161911). Plays a role in osteogenesis
CC (PubMed:25892096). {ECO:0000250|UniProtKB:Q12802,
CC ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:20139090,
CC ECO:0000269|PubMed:23658642, ECO:0000269|PubMed:24161911,
CC ECO:0000269|PubMed:25892096}.
CC -!- SUBUNIT: Interacts with the cAMP-dependent protein kinase (PKA)
CC holoenzyme and with the regulatory subunit PRKAR2A (PubMed:21102438,
CC PubMed:24161911, PubMed:23658642). Interacts with RHOA. Interacts also
CC with RHOB and RHOC. Identified in a ternary complex with RHOA and
CC PRKAR2A. Identified in a complex with NR3C1 and RHOA (By similarity).
CC Interacts with BRAF and KSR1. Identified in a complex with BRAF and
CC KSR1 (PubMed:21102438). Component of a signaling complex containing at
CC least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13
CC interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and
CC ZAK. Interacts (phosphorylated form) with YWHAB and YWHAZ. Interaction
CC with YWHAB inhibits activation of RHOA, interferes with PKN1 binding
CC and activation of MAP kinases. Interacts with GNA12 (By similarity).
CC Interacts with IKBKB (PubMed:23090968). Interacts with ESR1, THRA,
CC PPARA and NME2 (By similarity). Interacts (via the C-terminal domain
CC after the PH domain) with MEF2C and RXRB (PubMed:20139090). Interacts
CC (via the C-terminal domain after the PH domain) with PRKD1
CC (PubMed:23658642, PubMed:24161911). {ECO:0000250|UniProtKB:Q12802,
CC ECO:0000269|PubMed:20139090, ECO:0000269|PubMed:21102438,
CC ECO:0000269|PubMed:23090968, ECO:0000269|PubMed:23658642,
CC ECO:0000269|PubMed:24161911}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q12802}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q12802}. Cytoplasm, cell cortex
CC {ECO:0000250|UniProtKB:Q12802}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:20139090}. Nucleus {ECO:0000250|UniProtKB:Q12802}.
CC Membrane {ECO:0000250|UniProtKB:Q12802}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q12802}. Note=Colocalizes with actin and myosin
CC filaments in developing cardiomyocytes (PubMed:20139090). Colocalizes
CC with the actin cytoskeleton at the cell cortex (By similarity).
CC {ECO:0000250|UniProtKB:Q12802, ECO:0000269|PubMed:20139090}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=E9Q394-1; Sequence=Displayed;
CC Name=2;
CC IsoId=E9Q394-2; Sequence=VSP_058344, VSP_058345;
CC -!- TISSUE SPECIFICITY: Detected in embryonic heart, limb bud, first
CC branchial arch and forebrain (at protein level) (PubMed:20139090).
CC Detected in heart (PubMed:20139090). Detected in perichondrium, but not
CC in the bone growth plate (PubMed:25892096).
CC {ECO:0000269|PubMed:20139090, ECO:0000269|PubMed:25892096}.
CC -!- DEVELOPMENTAL STAGE: Detected in head folds, notochord and somites at
CC 8.5 dpc, with little or no expression in the looping heart. Detected in
CC heart, vasculature, eye, ear, somites, gut and brain at 9.5 dpc.
CC Expression in the heart increases by 10.5 dpc. Highly expressed in
CC atrial and ventricular myocardium and endocardium, trabeculae and
CC outflow tract at 14.5 dpc. Additionally, detected in skeletal muscle,
CC tongue, gut, kidney, lung, urinary system and in the choroid plexus of
CC the brain. {ECO:0000269|PubMed:23658642}.
CC -!- INDUCTION: Up-regulated in the left heart ventricle in response to
CC phenylephrine. {ECO:0000269|PubMed:17537920}.
CC -!- DOMAIN: The DH domain is sufficient for interaction with RHOA, and for
CC guanine nucleotide exchange (GEF) activity with RHOA. Forms that lack
CC C-terminal regulatory domains have transforming activity and function
CC as oncogenes. {ECO:0000250|UniProtKB:Q12802}.
CC -!- DOMAIN: The PH domain does not play a role in lipid-binding. Instead,
CC it inhibits the guanine nucleotide exchange (GEF) activity of the
CC isolated DH domain (in vitro). {ECO:0000250|UniProtKB:Q12802}.
CC -!- DOMAIN: The C-terminal domain after the PH domain is involved in
CC protein-protein interactions that are required for normal, compensatory
CC cardiac hypertrophy in response to pressure overload.
CC {ECO:0000269|PubMed:24161911}.
CC -!- DISRUPTION PHENOTYPE: Complete embryonic lethality (PubMed:16469733,
CC PubMed:20139090). Mutant embryos are present at the expected Mendelian
CC rate and develop normally up to 8 dpc. At 10 dpc, mutant embryos appear
CC smaller, have an enlarged heart and pericardiac effusion. The
CC myocardium is thinner than normal and has reduced trabeculation.
CC Sarcomeres are abnormal with incompleteley formed myofilaments that end
CC blindly and do not form Z-disks, indicating a defect in cardiomyocyte
CC differentiation (PubMed:20139090). Heterozygous mice are born at the
CC expected Mendelian frequency and appear grossly normal
CC (PubMed:16469733, PubMed:20139090). Heterozygous mice display a blunted
CC response to glucocorticoids (PubMed:16469733). Heterozygous mice
CC display reduced bone volume relative to body size, but no change of
CC bone length. Heterozygous mice display reduced bone mineral density and
CC reduced trabecular bone, similar to osteoporotic bone. The number of
CC osteoblasts in trabecular bone is reduced (PubMed:25892096).
CC {ECO:0000269|PubMed:16469733, ECO:0000269|PubMed:20139090,
CC ECO:0000269|PubMed:25892096}.
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DR EMBL; AC113019; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC158749; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK149507; BAE28926.1; -; mRNA.
DR CCDS; CCDS52276.1; -. [E9Q394-1]
DR RefSeq; NP_083608.1; NM_029332.1. [E9Q394-1]
DR RefSeq; XP_006541318.1; XM_006541255.3. [E9Q394-2]
DR SMR; E9Q394; -.
DR STRING; 10090.ENSMUSP00000117686; -.
DR iPTMnet; E9Q394; -.
DR PhosphoSitePlus; E9Q394; -.
DR EPD; E9Q394; -.
DR jPOST; E9Q394; -.
DR MaxQB; E9Q394; -.
DR PaxDb; E9Q394; -.
DR PeptideAtlas; E9Q394; -.
DR PRIDE; E9Q394; -.
DR ProteomicsDB; 296158; -. [E9Q394-1]
DR ProteomicsDB; 296159; -. [E9Q394-2]
DR Antibodypedia; 15576; 202 antibodies from 29 providers.
DR Ensembl; ENSMUST00000166315; ENSMUSP00000129784; ENSMUSG00000066406. [E9Q394-1]
DR GeneID; 75547; -.
DR KEGG; mmu:75547; -.
DR UCSC; uc009hwq.1; mouse.
DR UCSC; uc009hwx.2; mouse. [E9Q394-1]
DR CTD; 11214; -.
DR MGI; MGI:2676556; Akap13.
DR VEuPathDB; HostDB:ENSMUSG00000066406; -.
DR eggNOG; KOG3520; Eukaryota.
DR GeneTree; ENSGT00940000154146; -.
DR OMA; XDQKSTV; -.
DR Reactome; R-MMU-193648; NRAGE signals death through JNK.
DR Reactome; R-MMU-416482; G alpha (12/13) signalling events.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013026; RHOB GTPase cycle.
DR Reactome; R-MMU-9013106; RHOC GTPase cycle.
DR BioGRID-ORCS; 75547; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Akap13; mouse.
DR PRO; PR:E9Q394; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; E9Q394; protein.
DR Bgee; ENSMUSG00000066406; Expressed in mesenteric lymph node and 220 other tissues.
DR ExpressionAtlas; E9Q394; baseline and differential.
DR Genevisible; E9Q394; MM.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; IEA:InterPro.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0005078; F:MAP-kinase scaffold activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0060090; F:molecular adaptor activity; ISS:UniProtKB.
DR GO; GO:0051018; F:protein kinase A binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0086023; P:adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process; IMP:UniProtKB.
DR GO; GO:0071875; P:adrenergic receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0060348; P:bone development; IMP:UniProtKB.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:0061049; P:cell growth involved in cardiac muscle cell development; ISO:MGI.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:UniProtKB.
DR GO; GO:0051168; P:nuclear export; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:MGI.
DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; ISS:UniProtKB.
DR GO; GO:1900169; P:regulation of glucocorticoid mediated signaling pathway; IMP:MGI.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0060297; P:regulation of sarcomere organization; IMP:UniProtKB.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR028852; AKAP13.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR041020; PH_16.
DR InterPro; IPR001849; PH_domain.
DR PANTHER; PTHR13944:SF18; PTHR13944:SF18; 1.
DR Pfam; PF17838; PH_16; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Cytoskeleton;
KW Guanine-nucleotide releasing factor; Membrane; Metal-binding; Methylation;
KW Nucleus; Phosphoprotein; Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..2776
FT /note="A-kinase anchor protein 13"
FT /id="PRO_0000436319"
FT DOMAIN 1957..2154
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 2194..2296
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 1754..1801
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 371..401
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 452..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 493..515
FT /note="Important for interaction with PRKAR2A"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT REGION 547..584
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 618..641
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 653..689
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 760..871
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 910..951
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 995..1029
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1431..1508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1527..1546
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1552..1678
FT /note="Important for interaction with MAP2K3"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT REGION 1565..1603
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1711..1756
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1882..2776
FT /note="Interaction with ESR1"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT REGION 2436..2471
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2549..2605
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2626..2776
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 2308..2345
FT /evidence="ECO:0000255"
FT COILED 2532..2646
FT /evidence="ECO:0000255"
FT COMPBIAS 486..500
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 624..641
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 653..676
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 764..814
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 818..833
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 844..871
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 920..937
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1004..1028
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1431..1477
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1578..1603
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1720..1753
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2442..2465
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2556..2605
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2626..2641
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2666..2697
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2716..2738
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 784
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT MOD_RES 809
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT MOD_RES 941
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1455
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT MOD_RES 1473
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT MOD_RES 1507
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT MOD_RES 1532
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT MOD_RES 1569
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1M3G7"
FT MOD_RES 1608
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1611
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1613
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1637
FT /note="N6-methyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT MOD_RES 1839
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 1858
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT MOD_RES 1892
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1893
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT MOD_RES 1895
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1908
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1M3G7"
FT MOD_RES 2308
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1M3G7"
FT MOD_RES 2361
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2431
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT MOD_RES 2527
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2530
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 2673
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12802"
FT MOD_RES 2692
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1307..1311
FT /note="GKQGK -> E (in isoform 2)"
FT /id="VSP_058344"
FT VAR_SEQ 1548..1565
FT /note="Missing (in isoform 2)"
FT /id="VSP_058345"
SQ SEQUENCE 2776 AA; 303976 MW; 1A27E2B4986306EE CRC64;
MKLSPQQAPL YGDCVVTVLL AEEDKVEDDA IFYLIFSGST LYHCTSTRKV SSDTLETIAP
GHDCCETVKV LLCASREGLP VFVVAEEDFH FVQDEAYDAA QFLATSAGNQ QALNFTRFLD
RSGPPSRDVN SLDEKVALAF RHLKLPAEWN VLGTDHTLHD GGPRETLMHF AVRLGLLRLT
WFLLQKPGGR GALSIHNKEG ATPVSLALER GYHELHQLLT EENAGEPDSW SSLSYEIPYG
DCSVRHHREL DIYTLTSESE SHREPHGDSC TGHISKLMNI QQQLMKTNLK QMDNLMPLMV
TAQDSSCVPS VPETDGLFLP CVPEPSDHQH PPFEETKSTL CCQRSPGRMA ESSCDLSSMV
EEENVICSHK KNKDVGRKGE EAEPASAMDS GSASHQDSCL QSVPDCGVKG REGLPSCGNR
NEVTGTNYSG VATCQQPLSS RSSVLQDAMV TEPDACQHSS GRELPDSSST DVGAPEKAGE
LEHSLLTPDA TTQNNKPQVG EGTKERLENS DSSTTETTAV QVLSEPMEKA DITNHVFATS
AVGVNTPAEA SPALSSEEIP TEKPGMETQE RGCEGGTTSD QSSPVLPAAA IENKVLGGQE
PDTSIAGFCK TASPLDLTMP GPSSDGMPEQ NSESHARPAQ SLSGQALLCS TAEAGTPSAE
ATHQPSTVTS SGRLEECGSG KASLPESTMV QPSTQELCTT LCPEDPQADT VTSDTVKNTQ
KSVGVCHLCV SDAKNQGNGL KQDTPLTNVL EDVPRLPSVV SQTEKELAPD QVSPPASSFS
LASSPESESV TKDDALSLVP SQKEKGTATP QLHRTTACRD GPDGRDLSDT DKVGDGATDP
PPSSAVELRT SMGNTSPVGI GGEQEGSSPT ATLEVLSDSL LHNVDKAALV SDFTLPEEGV
SVVVPESSTA LGQDGKDRAM SCSSVKEDVH SSEMSREDQR TPPSGQEIPG LCEKPMSALC
AEEKAQQHTP SACLKTETKD IKEVAPQVSL LTEGGAAKSL VPPRTSLSAD SKQKASSTEQ
SGSSLLPSGL PGASEALHCN QPSALDVVVE NTQFQGETNA CEVSRSAMED VTVADASPAT
AEPRKKDASH CIKDIPISEL LNQEKQMTPS LPEAFLDKGV TDLQEVITPE IEPLDCKRET
LEGTDLNCAT SNSKETPIEK PMQPLARDLP TETGLSVINN NVPQADMKQV AQASIPAEES
NATTVSTQAA DVPTRADSIE ETATRIVEAV IRQVRASNAL MAKVETQNPS LSSPETKQLE
NAYTESACAF LPGETPQIEK THEDTTGQCG AETEEPEKII LPESAPGKQG KMPDTRTGDE
VDLLSRISAA SEEEAVGNGA ATPKMKQGPG TQAINRESWC AIEPCPEAAS LLASKQSSEC
RSFIDVGLGT ECASKEGMLQ RVSGSESDLF HSPSDEMDSI IFPKPEEEQL LCDTTGSSSS
TDDTASLDRH SSHGSDVSLP QTSKLNRSRN HQSANGFFSP GVEAPESRES ESEPAGSGEM
EEEEMDSITE VPANCSFLRS SMRSLSPFRR HSWGPGKNAA SDAEMNQRSS MRALGHVVRR
PPIHRRSFSL EGLTGGGVGN KPSSSLEMSS ANSSELRNPF GGEEQRNSLM SLSEEHLEPD
QRQHHRMFDQ QTCYRSKQQG FNYCTSAISS PLTKSISLMT ISHPGLDSSR PFHSTSANLT
ESITEENCNF LPPSPSKKNF EEKSGTKVSR TFSYIRNKMS SSKKSKEKEK EKDKIKEKEK
DSKEKEKDKK TLNGHTFSPI PIVGPISCSQ CMKPFTNKDA YTCAGCGAFV HKGCRENLAS
CAKVKMKQPK GSLQAHDTSS LPTVIMRNKS SQPKERPRSA VLLADEATAA PMFTNRRSQQ
SVSLSKSVSI QNITGVGNDE NMSNTWKFLS HSTDSLNKIC KVNESTESLT DEGVGTDMNE
GQLMGDFESD SKQLEAESWS RTVDSKFLKQ QKKDVVKRQE VIYELMQTEL HHIRTLKIMS
DVYSRGMMTD LLFEQQMVEK LFPCLDELIS IHSQFFQRIL ERKKESLVDK SEKNFLIKRI
GDVLVSQFSG ESAERLKKTY GKFCGQHNQS VNYFKDLYTK DKRFQAFVKK KMSSSVVRRL
GIPECILLVT QRITKYPVLF QRILQCTKDN EVEQEDLTQS LSLVKDVIGA VDSKVASYEK
KVRLGEIYTK TDSKSIMRMK SGQMFAKEDL RRKKLVRDGS VFLKSTTGRL KEVQAVLLTD
ILVFLQEKDQ KYVFASLDHK STVISLKKLI VREVAHEEKG LFLISMGVKD PEMVEVHASS
REERNSWIQI IQDTINSLNR DEDEGIPSEN EEEKKLLDTK ARELKEQLQQ KDQQILLLLE
EKEMIFRDMT ECSTPLPEDC SPTHSPRVLF RSNTEEALKG GPLMKSAINE VEILQSLVSG
SLGGTLGQSI SSPVEQEVMA APISLPRRAE TFGGFDCHQM NASKGGEKEE GDDGQDLRRT
ESDSGLKKGG NGNLVFMLKR NSEQVVQSIV HLHELLSMLQ GVVLQQDSYI EDQKLVLTEK
VLTRSASRPS SLIEQEKQRS LEKQRQDLAN LQKQQAQHLE EKRRREREWE AREQELRDRE
AKLAEREETV RRRQQDLERD REELQQKKGT YQCDLERLRA AQKQLEREQE QLRRDTERLS
QRQMDQNLCQ VSNKHGRLMR IPSFLPNSDE FSSPSAPSVT KSGSLDSELS VSPKRNSISR
TQKDKGPFHI LGSASQTKVP EGQSQAPSST STSTRLFGLS KPKEKKEKKK KSKGSRTQPG
DGPASEVPAE GEEIFC
