AKP13_HUMAN
ID AKP13_HUMAN Reviewed; 2813 AA.
AC Q12802; Q14572; Q59FP6; Q86W90; Q8WXQ6; Q96JP6; Q96P79; Q9Y5T0; Q9Y5T6;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=A-kinase anchor protein 13;
DE Short=AKAP-13;
DE AltName: Full=AKAP-Lbc {ECO:0000303|PubMed:11546812};
DE AltName: Full=Breast cancer nuclear receptor-binding auxiliary protein {ECO:0000303|PubMed:9627117};
DE AltName: Full=Guanine nucleotide exchange factor Lbc;
DE AltName: Full=Human thyroid-anchoring protein 31 {ECO:0000303|PubMed:11696353};
DE AltName: Full=Lymphoid blast crisis oncogene {ECO:0000303|PubMed:24993829};
DE Short=LBC oncogene {ECO:0000303|PubMed:24993829};
DE AltName: Full=Non-oncogenic Rho GTPase-specific GTP exchange factor;
DE AltName: Full=Protein kinase A-anchoring protein 13;
DE Short=PRKA13;
DE AltName: Full=p47;
GN Name=AKAP13;
GN Synonyms=BRX {ECO:0000303|PubMed:9627117},
GN HT31 {ECO:0000303|PubMed:11696353}, LBC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND VARIANTS
RP CYS-574 AND SER-2457.
RX PubMed=11696353; DOI=10.1016/s0014-5793(01)02995-7;
RA Klussmann E., Edemir B., Pepperle B., Tamma G., Henn V., Klauschenz E.,
RA Hundsrucker C., Maric K., Rosenthal W.;
RT "Ht31: the first protein kinase A anchoring protein to integrate protein
RT kinase A and Rho signaling.";
RL FEBS Lett. 507:264-268(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, INTERACTION WITH PKA HOLOENZYME; PRKAR2A; GNA12; RHOA;
RP RHOB AND RHOC, IDENTIFICATION IN A COMPLEX WITH RHOA AND PRKAR2A,
RP MUTAGENESIS OF ALA-1251; ILE-1260 AND TYR-2153, AND VARIANTS VAL-624;
RP MET-897 AND SER-2457.
RX PubMed=11546812; DOI=10.1074/jbc.m106629200;
RA Diviani D., Soderling J., Scott J.D.;
RT "AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-
RT mediated stress fiber formation.";
RL J. Biol. Chem. 276:44247-44257(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS THR-452; ARG-494;
RP CYS-574; LYS-689; ALA-845; MET-897; ALA-1062; ASN-1086 AND THR-1216.
RC TISSUE=Lung;
RA Miyamoto M., Ono Y.;
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Hippocampus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1385-2813 (ISOFORM 1), FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, INTERACTION WITH ESR1; THRA AND PPARA, AND
RP VARIANT SER-2457.
RC TISSUE=Testis;
RX PubMed=9627117; DOI=10.1038/sj.onc.1201783;
RA Rubino D., Driggers P., Arbit D., Kemp L., Miller B., Coso O., Pagliai K.,
RA Gray K., Gutkind S., Segars J.;
RT "Characterization of Brx, a novel Dbl family member that modulates estrogen
RT receptor action.";
RL Oncogene 16:2513-2526(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1827-2813 (ISOFORM 3), FUNCTION, SUBCELLULAR
RP LOCATION, DOMAIN, AND TISSUE SPECIFICITY.
RC TISSUE=Skeletal muscle;
RX PubMed=9891067; DOI=10.1128/mcb.19.2.1334;
RA Sterpetti P., Hack A.A., Bashar M.P., Park B., Cheng S.-D., Knoll J.H.M.,
RA Urano T., Feig L.A., Toksoz D.;
RT "Activation of the Lbc Rho exchange factor proto-oncogene by truncation of
RT an extended C terminus that regulates transformation and targeting.";
RL Mol. Cell. Biol. 19:1334-1345(1999).
RN [7]
RP ERRATUM OF PUBMED:9891067.
RA Sterpetti P., Hack A.A., Bashar M.P., Park B., Cheng S.D., Knoll J.H.,
RA Urano T., Feig L.A., Toksoz D.;
RL Mol. Cell. Biol. 19:3930-3930(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1913-2335 (ISOFORM 3).
RX PubMed=8290273;
RA Toksoz D., Williams D.A.;
RT "Novel human oncogene lbc detected by transfection with distinct homology
RT regions to signal transduction products.";
RL Oncogene 9:621-628(1994).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 754-1768, INTERACTION WITH PKA HOLOENZYME AND
RP PRKAR2A, AND MUTAGENESIS OF ALA-1265.
RC TISSUE=Thyroid;
RX PubMed=1618839; DOI=10.1016/s0021-9258(18)42221-1;
RA Carr D.W., Hausken Z.E., Fraser I.D.C., Stofko-Hahn R.E., Scott J.D.;
RT "Association of the type II cAMP-dependent protein kinase with a human
RT thyroid RII-anchoring protein. Cloning and characterization of the RII-
RT binding domain.";
RL J. Biol. Chem. 267:13376-13382(1992).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1486-2813 (ISOFORM 3), AND
RP VARIANT SER-2457.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP FUNCTION IN ACTIVATION OF ESR2.
RX PubMed=11579095; DOI=10.1074/jbc.m106927200;
RA Driggers P.H., Segars J.H., Rubino D.M.;
RT "The proto-oncoprotein Brx activates estrogen receptor beta by a p38
RT mitogen-activated protein kinase pathway.";
RL J. Biol. Chem. 276:46792-46797(2001).
RN [12]
RP INTERACTION WITH NME2.
RX PubMed=15249197; DOI=10.1016/j.bbrc.2004.06.067;
RA Iwashita S., Fujii M., Mukai H., Ono Y., Miyamoto M.;
RT "Lbc proto-oncogene product binds to and could be negatively regulated by
RT metastasis suppressor nm23-H2.";
RL Biochem. Biophys. Res. Commun. 320:1063-1068(2004).
RN [13]
RP FUNCTION, INTERACTION WITH YWHAB; YWHAZ AND PKA, PHOSPHORYLATION AT
RP SER-1565, AND MUTAGENESIS OF ALA-1251; ILE-1260 AND SER-1565.
RX PubMed=15229649; DOI=10.1038/sj.emboj.7600287;
RA Diviani D., Abuin L., Cotecchia S., Pansier L.;
RT "Anchoring of both PKA and 14-3-3 inhibits the Rho-GEF activity of the
RT AKAP-Lbc signaling complex.";
RL EMBO J. 23:2811-2820(2004).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1565, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [15]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH NR3C1 AND RHOA.
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-983 AND SER-2728, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [17]
RP FUNCTION, AND INTERACTION WITH RHOA.
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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-983; SER-1645; SER-1647;
RP SER-1876; SER-1929; SER-1932; SER-2398; SER-2703; SER-2709 AND SER-2728,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-983; SER-1642; SER-1645;
RP SER-1647; SER-1876 AND SER-2728, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [22]
RP FUNCTION, AND INTERACTION WITH KSR1; BRAF; PKA CATALYTIC SUBUNIT AND
RP 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 [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-790; SER-983 AND SER-1929,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP FUNCTION, INTERACTION WITH PKN1; YWHAB; MAPK14 AND ZAK, IDENTIFICATION IN A
RP COMPLEX WITH PKN1; MAPK14; MAP2K3 AND ZAK, REGION, AND MUTAGENESIS OF
RP SER-1565.
RX PubMed=21224381; DOI=10.1074/jbc.m110.185645;
RA Cariolato L., Cavin S., Diviani D.;
RT "A-kinase anchoring protein (AKAP)-Lbc anchors a PKN-based signaling
RT complex involved in alpha1-adrenergic receptor-induced p38 activation.";
RL J. Biol. Chem. 286:7925-7937(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-983; SER-1642; SER-1645;
RP SER-1647; SER-1895; SER-1929; THR-1930; SER-1932; SER-2563 AND SER-2728,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-815; SER-983; SER-1507;
RP SER-1876; SER-1929; SER-1932; THR-2467; SER-2709 AND SER-2728, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP FUNCTION, INTERACTION WITH IKBKB, AND MUTAGENESIS OF TRP-2324.
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 [29]
RP FUNCTION.
RX PubMed=23716597; DOI=10.1128/mcb.00031-13;
RA Perez Lopez I., Cariolato L., Maric D., Gillet L., Abriel H., Diviani D.;
RT "A-kinase anchoring protein Lbc coordinates a p38 activating signaling
RT complex controlling compensatory cardiac hypertrophy.";
RL Mol. Cell. Biol. 33:2903-2917(2013).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1489; SER-1540; THR-2467;
RP SER-2473 AND SER-2728, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [31]
RP METHYLATION [LARGE SCALE ANALYSIS] AT LYS-1670, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [32]
RP STRUCTURE BY NMR OF 493-516 IN COMPLEX WITH PRKAR2A PEPTIDE, AND
RP INTERACTION WITH PRKAR2A.
RX PubMed=11285229; DOI=10.1093/emboj/20.7.1651;
RA Newlon M.G., Roy M., Morikis D., Carr D.W., Westphal R., Scott J.D.,
RA Jennings P.A.;
RT "A novel mechanism of PKA anchoring revealed by solution structures of
RT anchoring complexes.";
RL EMBO J. 20:1651-1662(2001).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1968-2338 IN COMPLEX WITH RHOA,
RP FUNCTION, INTERACTION WITH RHOA, DOMAIN, AND MUTAGENESIS OF GLN-2148;
RP LYS-2152 AND ASP-2189.
RX PubMed=25186459; DOI=10.1042/bj20140606;
RA Abdul Azeez K.R., Knapp S., Fernandes J.M., Klussmann E., Elkins J.M.;
RT "The crystal structure of the RhoA-AKAP-Lbc DH-PH domain complex.";
RL Biochem. J. 464:231-239(2014).
RN [34]
RP STRUCTURE BY NMR OF 2164-2346, FUNCTION, INTERACTION WITH RHOA, DOMAIN, AND
RP MUTAGENESIS OF GLU-2001; ARG-2136; ARG-2289 AND PHE-2299.
RX PubMed=24993829; DOI=10.1074/jbc.m114.561787;
RA Lenoir M., Sugawara M., Kaur J., Ball L.J., Overduin M.;
RT "Structural insights into the activation of the RhoA GTPase by the lymphoid
RT blast crisis (Lbc) oncoprotein.";
RL J. Biol. Chem. 289:23992-24004(2014).
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 (PubMed:11546812, PubMed:15229649, PubMed:23090968,
CC PubMed:25186459, PubMed:24993829). May also activate other Rho family
CC members (PubMed:11546812). Part of a kinase signaling complex that
CC links ADRA1A and ADRA1B adrenergic receptor signaling to the activation
CC of downstream p38 MAP kinases, such as MAPK11 and MAPK14
CC (PubMed:17537920, PubMed:23716597, PubMed:21224381). Part of a
CC signaling complex that links ADRA1B signaling to the activation of RHOA
CC and IKBKB/IKKB, leading to increased NF-kappa-B transcriptional
CC activity (PubMed:23090968). Part of a RHOA-dependent signaling cascade
CC that mediates responses to lysophosphatidic acid (LPA), a signaling
CC molecule that activates G-protein coupled receptors and potentiates
CC transcriptional activation of the glucocorticoid receptor NR3C1
CC (PubMed:16469733). Part of a signaling cascade that stimulates MEF2C-
CC dependent gene expression in response to lysophosphatidic acid (LPA)
CC (By similarity). Part of a signaling pathway that activates MAPK11
CC and/or MAPK14 and leads to increased transcription activation of the
CC estrogen receptors ESR1 and ESR2 (PubMed:9627117, PubMed:11579095).
CC Part 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
CC (PubMed:21102438). Functions as scaffold protein that anchors cAMP-
CC dependent protein kinase (PKA) and PRKD1. This promotes activation of
CC PRKD1, leading to increased phosphorylation of HDAC5 and ultimately
CC cardiomyocyte hypertrophy (By similarity). Has no guanine nucleotide
CC exchange activity on CDC42, Ras or Rac (PubMed:11546812). Required for
CC normal embryonic heart development, and in particular for normal
CC sarcomere formation in the developing cardiomyocytes (By similarity).
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:17537920, PubMed:23090968). Required for
CC normal adaptive cardiac hypertrophy in response to pressure overload
CC (PubMed:23716597). Plays a role in osteogenesis (By similarity).
CC {ECO:0000250|UniProtKB:E9Q394, ECO:0000269|PubMed:11546812,
CC ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:17537920,
CC ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:23716597,
CC ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:25186459,
CC ECO:0000269|PubMed:9627117, ECO:0000269|PubMed:9891067}.
CC -!- SUBUNIT: Interacts with the cAMP-dependent protein kinase (PKA)
CC holoenzyme and with the regulatory subunit PRKAR2A (PubMed:11546812,
CC PubMed:1618839, PubMed:15229649, PubMed:21102438, PubMed:11285229).
CC Interacts with RHOA (PubMed:11546812, PubMed:17537920, PubMed:25186459,
CC PubMed:24993829). Interacts also with RHOB and RHOC (PubMed:11546812).
CC Identified in a ternary complex with RHOA and PRKAR2A
CC (PubMed:11546812). Identified in a complex with NR3C1 and RHOA
CC (PubMed:16469733). Interacts with BRAF and KSR1 (PubMed:21102438).
CC Identified in a complex with BRAF and KSR1 (PubMed:21102438). Component
CC of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK
CC and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1,
CC which in turn recruits MAPK14, MAP2K3 and ZAK (PubMed:21224381).
CC Interacts (phosphorylated form) with YWHAB and YWHAZ (PubMed:15229649,
CC PubMed:21224381). Interaction with YWHAB inhibits activation of RHOA,
CC interferes with PKN1 binding and activation of MAP kinases
CC (PubMed:15229649, PubMed:21224381). Interacts with GNA12
CC (PubMed:11546812). Interacts with IKBKB (PubMed:23090968). Interacts
CC with ESR1, THRA, PPARA and NME2 (PubMed:9627117, PubMed:15249197).
CC Interacts (via the C-terminal domain after the PH domain) with MEF2C
CC and RXRB. Interacts (via the C-terminal domain after the PH domain)
CC with PRKD1 (By similarity). {ECO:0000250|UniProtKB:E9Q394,
CC ECO:0000269|PubMed:11285229, ECO:0000269|PubMed:11546812,
CC ECO:0000269|PubMed:11579095, ECO:0000269|PubMed:15229649,
CC ECO:0000269|PubMed:15249197, ECO:0000269|PubMed:1618839,
CC ECO:0000269|PubMed:17537920, ECO:0000269|PubMed:21102438,
CC ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:24993829,
CC ECO:0000269|PubMed:25186459, ECO:0000269|PubMed:9627117}.
CC -!- INTERACTION:
CC Q12802; P03372: ESR1; NbExp=3; IntAct=EBI-1373806, EBI-78473;
CC Q12802; Q9H492: MAP1LC3A; NbExp=2; IntAct=EBI-1373806, EBI-720768;
CC Q12802; P21980: TGM2; NbExp=4; IntAct=EBI-1373806, EBI-727668;
CC Q12802; P63104: YWHAZ; NbExp=2; IntAct=EBI-1373806, EBI-347088;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:11546812,
CC ECO:0000269|PubMed:9891067}. Cytoplasm {ECO:0000269|PubMed:9627117}.
CC Cytoplasm, cell cortex {ECO:0000269|PubMed:11546812}. Nucleus
CC {ECO:0000269|PubMed:9627117}. Membrane {ECO:0000269|PubMed:11696353,
CC ECO:0000269|PubMed:9891067}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11696353, ECO:0000305|PubMed:9891067}.
CC Note=Colocalizes with the actin cytoskeleton at the cell cortex.
CC {ECO:0000269|PubMed:11546812}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q12802-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q12802-2; Sequence=VSP_023490;
CC Name=3;
CC IsoId=Q12802-4; Sequence=VSP_023489, VSP_023491;
CC Name=4;
CC IsoId=Q12802-5; Sequence=VSP_023486, VSP_023487;
CC -!- TISSUE SPECIFICITY: Detected in mammary gland (PubMed:9627117).
CC Detected in heart (at protein level) (PubMed:11546812). Expressed as a
CC 5.3 kb transcript in hematopoietic cells, skeletal muscle, lung, heart,
CC estrogen-responsive reproductive tissues, including breast ductal
CC epithelium. Also found in testis and breast cancer cell lines.
CC Predominantly expressed as a 10 kb transcript in the heart and at lower
CC levels in the lung, placenta, kidney, pancreas, skeletal muscle and
CC liver. Transcripts of between 6-9 kb are also expressed in myeloid and
CC lymphoid lineages, a variety of epithelial tissues, and in skeletal
CC muscle. {ECO:0000269|PubMed:11546812, ECO:0000269|PubMed:9627117,
CC ECO:0000269|PubMed:9891067}.
CC -!- DOMAIN: The DH domain is sufficient for interaction with RHOA, and for
CC guanine nucleotide exchange (GEF) activity with RHOA (PubMed:24993829).
CC Forms that lack C-terminal regulatory domains have transforming
CC activity and function as oncogenes (PubMed:9891067).
CC {ECO:0000269|PubMed:24993829, ECO:0000269|PubMed:9891067,
CC ECO:0000305|PubMed:25186459}.
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:0000269|PubMed:24993829}.
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:0000250|UniProtKB:E9Q394}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50065.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC50065.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC Sequence=AAD21311.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAD40799.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD40799.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=AAL40923.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF387101; AAL40923.1; ALT_FRAME; mRNA.
DR EMBL; AF406992; AAL11723.1; -; mRNA.
DR EMBL; AB055890; BAB62913.1; -; mRNA.
DR EMBL; BC050312; AAH50312.1; -; mRNA.
DR EMBL; AF126008; AAD21311.1; ALT_FRAME; mRNA.
DR EMBL; AF127481; AAD40799.1; ALT_SEQ; mRNA.
DR EMBL; U03634; AAC50065.1; ALT_SEQ; mRNA.
DR EMBL; M90360; AAA58670.1; ALT_TERM; mRNA.
DR EMBL; AB209414; BAD92651.1; -; mRNA.
DR CCDS; CCDS32319.1; -. [Q12802-1]
DR CCDS; CCDS32320.1; -. [Q12802-2]
DR PIR; A42915; A42915.
DR PIR; I38434; I38434.
DR RefSeq; NP_001257475.1; NM_001270546.1.
DR RefSeq; NP_006729.4; NM_006738.5. [Q12802-2]
DR RefSeq; NP_009131.2; NM_007200.4. [Q12802-1]
DR PDB; 2DRN; NMR; -; C=1246-1269.
DR PDB; 2LG1; NMR; -; A=2164-2346.
DR PDB; 4D0N; X-ray; 2.10 A; B=1968-2338.
DR PDB; 4D0O; X-ray; 2.75 A; A/B=1972-2207.
DR PDB; 6BCA; X-ray; 2.00 A; A/B=2193-2333.
DR PDBsum; 2DRN; -.
DR PDBsum; 2LG1; -.
DR PDBsum; 4D0N; -.
DR PDBsum; 4D0O; -.
DR PDBsum; 6BCA; -.
DR BMRB; Q12802; -.
DR SMR; Q12802; -.
DR BioGRID; 116383; 71.
DR CORUM; Q12802; -.
DR DIP; DIP-180N; -.
DR IntAct; Q12802; 47.
DR MINT; Q12802; -.
DR STRING; 9606.ENSP00000354718; -.
DR ChEMBL; CHEMBL4523643; -.
DR GlyGen; Q12802; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q12802; -.
DR PhosphoSitePlus; Q12802; -.
DR BioMuta; AKAP13; -.
DR DMDM; 134048676; -.
DR EPD; Q12802; -.
DR jPOST; Q12802; -.
DR MassIVE; Q12802; -.
DR MaxQB; Q12802; -.
DR PaxDb; Q12802; -.
DR PeptideAtlas; Q12802; -.
DR PRIDE; Q12802; -.
DR ProteomicsDB; 58955; -. [Q12802-1]
DR ProteomicsDB; 58956; -. [Q12802-2]
DR ProteomicsDB; 58957; -. [Q12802-4]
DR ProteomicsDB; 58958; -. [Q12802-5]
DR Antibodypedia; 15576; 202 antibodies from 29 providers.
DR DNASU; 11214; -.
DR Ensembl; ENST00000361243.6; ENSP00000354718.2; ENSG00000170776.22. [Q12802-2]
DR Ensembl; ENST00000394518.7; ENSP00000378026.3; ENSG00000170776.22. [Q12802-1]
DR Ensembl; ENST00000560302.5; ENSP00000453634.1; ENSG00000170776.22. [Q12802-5]
DR GeneID; 11214; -.
DR KEGG; hsa:11214; -.
DR MANE-Select; ENST00000394518.7; ENSP00000378026.3; NM_007200.5; NP_009131.2.
DR UCSC; uc002bls.5; human. [Q12802-1]
DR CTD; 11214; -.
DR DisGeNET; 11214; -.
DR GeneCards; AKAP13; -.
DR HGNC; HGNC:371; AKAP13.
DR HPA; ENSG00000170776; Low tissue specificity.
DR MIM; 604686; gene.
DR neXtProt; NX_Q12802; -.
DR OpenTargets; ENSG00000170776; -.
DR PharmGKB; PA24665; -.
DR VEuPathDB; HostDB:ENSG00000170776; -.
DR eggNOG; KOG3520; Eukaryota.
DR GeneTree; ENSGT00940000154146; -.
DR HOGENOM; CLU_076791_0_0_1; -.
DR InParanoid; Q12802; -.
DR OMA; XDQKSTV; -.
DR OrthoDB; 69816at2759; -.
DR PhylomeDB; Q12802; -.
DR TreeFam; TF325887; -.
DR PathwayCommons; Q12802; -.
DR Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR Reactome; R-HSA-416482; G alpha (12/13) signalling events.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR SignaLink; Q12802; -.
DR SIGNOR; Q12802; -.
DR BioGRID-ORCS; 11214; 18 hits in 1080 CRISPR screens.
DR ChiTaRS; AKAP13; human.
DR EvolutionaryTrace; Q12802; -.
DR GeneWiki; AKAP13; -.
DR GenomeRNAi; 11214; -.
DR Pharos; Q12802; Tbio.
DR PRO; PR:Q12802; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q12802; protein.
DR Bgee; ENSG00000170776; Expressed in tendon of biceps brachii and 206 other tissues.
DR ExpressionAtlas; Q12802; baseline and differential.
DR Genevisible; Q12802; HS.
DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
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; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProtKB.
DR GO; GO:0051018; F:protein kinase A binding; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0086023; P:adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process; ISS:UniProtKB.
DR GO; GO:0071875; P:adrenergic receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0060348; P:bone development; ISS:UniProtKB.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0061049; P:cell growth involved in cardiac muscle cell development; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0051168; P:nuclear export; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IEA:Ensembl.
DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; IDA:UniProtKB.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0060297; P:regulation of sarcomere organization; ISS:UniProtKB.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR IDEAL; IID00210; -.
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 InterPro; IPR018459; RII-bd_1.
DR PANTHER; PTHR13944:SF18; PTHR13944:SF18; 1.
DR Pfam; PF17838; PH_16; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR Pfam; PF10522; RII_binding_1; 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 3D-structure; Alternative splicing; Coiled coil; Cytoplasm;
KW Guanine-nucleotide releasing factor; Membrane; Metal-binding; Methylation;
KW Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome; Zinc;
KW Zinc-finger.
FT CHAIN 1..2813
FT /note="A-kinase anchor protein 13"
FT /id="PRO_0000080963"
FT DOMAIN 1994..2191
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 2231..2333
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 1791..1838
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 304..400
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 415..439
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 494..516
FT /note="Important for interaction with PRKAR2A"
FT REGION 539..585
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 632..653
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 690..726
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 805..856
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 939..965
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1431..1455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1467..1542
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1585..1715
FT /note="Important for interaction with MAP2K3"
FT /evidence="ECO:0000269|PubMed:21224381"
FT REGION 1601..1638
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1755..1793
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1919..2813
FT /note="Interaction with ESR1"
FT /evidence="ECO:0000269|PubMed:9627117"
FT REGION 2466..2502
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2665..2813
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1758..1790
FT /evidence="ECO:0000255"
FT COILED 2345..2381
FT /evidence="ECO:0000255"
FT COILED 2568..2683
FT /evidence="ECO:0000255"
FT COMPBIAS 326..359
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 360..385
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 545..561
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 562..579
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 690..720
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1431..1447
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1467..1501
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1757..1790
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2478..2501
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2665..2689
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2713..2732
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2744..2774
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 790
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 815
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 953
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:E9Q394"
FT MOD_RES 983
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1489
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1507
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1540
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1565
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15229649,
FT ECO:0007744|PubMed:17081983"
FT MOD_RES 1602
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1M3G7"
FT MOD_RES 1642
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 1645
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692"
FT MOD_RES 1647
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692"
FT MOD_RES 1670
FT /note="N6-methyllysine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 1876
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 1895
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 1929
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1930
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 1932
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 1945
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1M3G7"
FT MOD_RES 2345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1M3G7"
FT MOD_RES 2398
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 2467
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 2473
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 2563
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 2566
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:E9Q394"
FT MOD_RES 2703
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 2709
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2728
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 160..179
FT /note="DAGPRETLMHFAVRLGLLRL -> GENLYDLQTHFKFVIFLLFF (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023486"
FT VAR_SEQ 180..2813
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023487"
FT VAR_SEQ 1581..1598
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8290273,
FT ECO:0000303|PubMed:9891067, ECO:0000303|Ref.10"
FT /id="VSP_023489"
FT VAR_SEQ 1583..1598
FT /note="SMRVLGDVVRRPPIHR -> MSWCPSGVQYSAGLSADFNY (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:11546812"
FT /id="VSP_023490"
FT VAR_SEQ 1950..1951
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8290273,
FT ECO:0000303|PubMed:9891067, ECO:0000303|Ref.10"
FT /id="VSP_023491"
FT VARIANT 452
FT /note="M -> T (in dbSNP:rs2061821)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_030925"
FT VARIANT 494
FT /note="W -> R (in dbSNP:rs2061822)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_030926"
FT VARIANT 526
FT /note="K -> Q (in dbSNP:rs34434221)"
FT /id="VAR_051986"
FT VARIANT 574
FT /note="R -> C (in dbSNP:rs2061824)"
FT /evidence="ECO:0000269|PubMed:11696353, ECO:0000269|Ref.3"
FT /id="VAR_030927"
FT VARIANT 624
FT /note="G -> V (in dbSNP:rs745191)"
FT /evidence="ECO:0000269|PubMed:11546812"
FT /id="VAR_030928"
FT VARIANT 689
FT /note="E -> K (in dbSNP:rs7177107)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_030929"
FT VARIANT 845
FT /note="V -> A (in dbSNP:rs4075256)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_030930"
FT VARIANT 897
FT /note="V -> M (in dbSNP:rs4075254)"
FT /evidence="ECO:0000269|PubMed:11546812, ECO:0000269|Ref.3"
FT /id="VAR_030931"
FT VARIANT 1062
FT /note="P -> A (in dbSNP:rs4843074)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_030932"
FT VARIANT 1086
FT /note="D -> N (in dbSNP:rs4843075)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_030933"
FT VARIANT 1216
FT /note="M -> T (in dbSNP:rs7162168)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_030934"
FT VARIANT 1525
FT /note="S -> G (in dbSNP:rs35079107)"
FT /id="VAR_051987"
FT VARIANT 2457
FT /note="G -> S (in dbSNP:rs2241268)"
FT /evidence="ECO:0000269|PubMed:11546812,
FT ECO:0000269|PubMed:11696353, ECO:0000269|PubMed:9627117,
FT ECO:0000269|Ref.10"
FT /id="VAR_030935"
FT VARIANT 2801
FT /note="A -> T (in dbSNP:rs2614668)"
FT /id="VAR_030936"
FT MUTAGEN 1251
FT /note="A->P: Abolishes interaction with PRKAR2A and leads
FT to constitutive activation of RHOA; when associated with P-
FT 1260."
FT /evidence="ECO:0000269|PubMed:11546812,
FT ECO:0000269|PubMed:15229649"
FT MUTAGEN 1260
FT /note="I->P: Abolishes interaction with PRKAR2Aand leads to
FT constitutive activation of RHOA; when associated with P-
FT 1251."
FT /evidence="ECO:0000269|PubMed:11546812,
FT ECO:0000269|PubMed:15229649"
FT MUTAGEN 1265
FT /note="A->P: Abolishes interaction with PRKAR2A."
FT /evidence="ECO:0000269|PubMed:1618839"
FT MUTAGEN 1565
FT /note="S->A: Abolishes interaction with YWHAB, leading to
FT constitutive activation of RHOA and MAPK14."
FT /evidence="ECO:0000269|PubMed:15229649,
FT ECO:0000269|PubMed:21224381"
FT MUTAGEN 2001
FT /note="E->A: Decreases guanyl nucleotide exchange activity
FT toward RHOA."
FT /evidence="ECO:0000269|PubMed:24993829"
FT MUTAGEN 2136
FT /note="R->G: Decreases guanyl nucleotide exchange activity
FT toward RHOA."
FT /evidence="ECO:0000269|PubMed:24993829"
FT MUTAGEN 2148
FT /note="Q->Y: Abolishes guanyl nucleotide exchange activity
FT toward RHOA."
FT /evidence="ECO:0000269|PubMed:25186459"
FT MUTAGEN 2152
FT /note="K->Y: Abolishes guanyl nucleotide exchange activity
FT toward RHOA."
FT /evidence="ECO:0000269|PubMed:25186459"
FT MUTAGEN 2153
FT /note="Y->F: Loss of guanyl nucleotide exchange activity
FT toward RHOA."
FT /evidence="ECO:0000269|PubMed:11546812"
FT MUTAGEN 2189
FT /note="D->A: Reduces guanyl nucleotide exchange activity
FT toward RHOA."
FT /evidence="ECO:0000269|PubMed:25186459"
FT MUTAGEN 2189
FT /note="D->Y: Abolishes guanyl nucleotide exchange activity
FT toward RHOA."
FT /evidence="ECO:0000269|PubMed:25186459"
FT MUTAGEN 2289
FT /note="R->A: Decreases guanyl nucleotide exchange activity
FT toward RHOA."
FT /evidence="ECO:0000269|PubMed:24993829"
FT MUTAGEN 2299
FT /note="F->A: Decreases guanyl nucleotide exchange activity
FT toward RHOA."
FT /evidence="ECO:0000269|PubMed:24993829"
FT MUTAGEN 2324
FT /note="W->L: Impairs interaction with IKBKB."
FT /evidence="ECO:0000269|PubMed:23090968"
FT CONFLICT 191
FT /note="G -> R (in Ref. 1; AAL40923)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="C -> R (in Ref. 1; AAL40923)"
FT /evidence="ECO:0000305"
FT CONFLICT 609
FT /note="A -> V (in Ref. 1; AAL40923)"
FT /evidence="ECO:0000305"
FT CONFLICT 614
FT /note="A -> T (in Ref. 1; AAL40923)"
FT /evidence="ECO:0000305"
FT CONFLICT 618
FT /note="S -> P (in Ref. 1; AAL40923)"
FT /evidence="ECO:0000305"
FT CONFLICT 619
FT /note="D -> A (in Ref. 2; AAL11723)"
FT /evidence="ECO:0000305"
FT CONFLICT 755
FT /note="M -> S (in Ref. 9; AAA58670)"
FT /evidence="ECO:0000305"
FT CONFLICT 1385..1387
FT /note="TQA -> MLY (in Ref. 5; AAD21311)"
FT /evidence="ECO:0000305"
FT CONFLICT 1547
FT /note="N -> H (in Ref. 10; BAD92651)"
FT /evidence="ECO:0000305"
FT CONFLICT 1766..1768
FT /note="EKE -> KKK (in Ref. 9; AAA58670)"
FT /evidence="ECO:0000305"
FT CONFLICT 1877
FT /note="A -> G (in Ref. 6; AAD40799)"
FT /evidence="ECO:0000305"
FT CONFLICT 1897
FT /note="Q -> E (in Ref. 6; AAD40799)"
FT /evidence="ECO:0000305"
FT CONFLICT 2035
FT /note="V -> D (in Ref. 5; AAD21311)"
FT /evidence="ECO:0000305"
FT CONFLICT 2488
FT /note="D -> G (in Ref. 5; AAD21311)"
FT /evidence="ECO:0000305"
FT CONFLICT 2667..2668
FT /note="QL -> HV (in Ref. 3; BAB62913 and 5; AAD21311)"
FT /evidence="ECO:0000305"
FT HELIX 1248..1263
FT /evidence="ECO:0007829|PDB:2DRN"
FT TURN 1264..1268
FT /evidence="ECO:0007829|PDB:2DRN"
FT STRAND 1973..1975
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 1976..1979
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 1982..1986
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 1990..2018
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 2020..2027
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 2032..2038
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 2042..2061
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 2078..2084
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 2087..2117
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 2119..2131
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 2135..2137
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 2139..2149
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 2150..2152
FT /evidence="ECO:0007829|PDB:4D0N"
FT HELIX 2153..2163
FT /evidence="ECO:0007829|PDB:4D0N"
FT TURN 2166..2168
FT /evidence="ECO:0007829|PDB:2LG1"
FT STRAND 2177..2181
FT /evidence="ECO:0007829|PDB:2LG1"
FT TURN 2182..2184
FT /evidence="ECO:0007829|PDB:2LG1"
FT HELIX 2186..2191
FT /evidence="ECO:0007829|PDB:2LG1"
FT HELIX 2194..2207
FT /evidence="ECO:0007829|PDB:6BCA"
FT STRAND 2213..2215
FT /evidence="ECO:0007829|PDB:6BCA"
FT STRAND 2221..2223
FT /evidence="ECO:0007829|PDB:6BCA"
FT HELIX 2224..2227
FT /evidence="ECO:0007829|PDB:6BCA"
FT STRAND 2232..2241
FT /evidence="ECO:0007829|PDB:6BCA"
FT STRAND 2247..2265
FT /evidence="ECO:0007829|PDB:6BCA"
FT STRAND 2268..2271
FT /evidence="ECO:0007829|PDB:6BCA"
FT STRAND 2275..2277
FT /evidence="ECO:0007829|PDB:2LG1"
FT STRAND 2279..2283
FT /evidence="ECO:0007829|PDB:6BCA"
FT STRAND 2286..2290
FT /evidence="ECO:0007829|PDB:6BCA"
FT STRAND 2297..2302
FT /evidence="ECO:0007829|PDB:6BCA"
FT STRAND 2304..2307
FT /evidence="ECO:0007829|PDB:4D0N"
FT STRAND 2309..2314
FT /evidence="ECO:0007829|PDB:6BCA"
FT HELIX 2318..2332
FT /evidence="ECO:0007829|PDB:6BCA"
SQ SEQUENCE 2813 AA; 307550 MW; 6A8FDAC9A3D3B1F2 CRC64;
MKLNPQQAPL YGDCVVTVLL AEEDKAEDDV VFYLVFLGST LRHCTSTRKV SSDTLETIAP
GHDCCETVKV QLCASKEGLP VFVVAEEDFH FVQDEAYDAA QFLATSAGNQ QALNFTRFLD
QSGPPSGDVN SLDKKLVLAF RHLKLPTEWN VLGTDQSLHD AGPRETLMHF AVRLGLLRLT
WFLLQKPGGR GALSIHNQEG ATPVSLALER GYHKLHQLLT EENAGEPDSW SSLSYEIPYG
DCSVRHHREL DIYTLTSESD SHHEHPFPGD GCTGPIFKLM NIQQQLMKTN LKQMDSLMPL
MMTAQDPSSA PETDGQFLPC APEPTDPQRL SSSEETESTQ CCPGSPVAQT ESPCDLSSIV
EEENTDRSCR KKNKGVERKG EEVEPAPIVD SGTVSDQDSC LQSLPDCGVK GTEGLSSCGN
RNEETGTKSS GMPTDQESLS SGDAVLQRDL VMEPGTAQYS SGGELGGIST TNVSTPDTAG
EMEHGLMNPD ATVWKNVLQG GESTKERFEN SNIGTAGASD VHVTSKPVDK ISVPNCAPAA
SSLDGNKPAE SSLAFSNEET STEKTAETET SRSREESADA PVDQNSVVIP AAAKDKISDG
LEPYTLLAAG IGEAMSPSDL ALLGLEEDVM PHQNSETNSS HAQSQKGKSS PICSTTGDDK
LCADSACQQN TVTSSGDLVA KLCDNIVSES ESTTARQPSS QDPPDASHCE DPQAHTVTSD
PVRDTQERAD FCPFKVVDNK GQRKDVKLDK PLTNMLEVVS HPHPVVPKME KELVPDQAVI
SDSTFSLANS PGSESVTKDD ALSFVPSQKE KGTATPELHT ATDYRDGPDG NSNEPDTRPL
EDRAVGLSTS STAAELQHGM GNTSLTGLGG EHEGPAPPAI PEALNIKGNT DSSLQSVGKA
TLALDSVLTE EGKLLVVSES SAAQEQDKDK AVTCSSIKEN ALSSGTLQEE QRTPPPGQDT
QQFHEKSISA DCAKDKALQL SNSPGASSAF LKAETEHNKE VAPQVSLLTQ GGAAQSLVPP
GASLATESRQ EALGAEHNSS ALLPCLLPDG SDGSDALNCS QPSPLDVGVK NTQSQGKTSA
CEVSGDVTVD VTGVNALQGM AEPRRENISH NTQDILIPNV LLSQEKNAVL GLPVALQDKA
VTDPQGVGTP EMIPLDWEKG KLEGADHSCT MGDAEEAQID DEAHPVLLQP VAKELPTDME
LSAHDDGAPA GVREVMRAPP SGRERSTPSL PCMVSAQDAP LPKGADLIEE AASRIVDAVI
EQVKAAGALL TEGEACHMSL SSPELGPLTK GLESAFTEKV STFPPGESLP MGSTPEEATG
SLAGCFAGRE EPEKIILPVQ GPEPAAEMPD VKAEDEVDFR ASSISEEVAV GSIAATLKMK
QGPMTQAINR ENWCTIEPCP DAASLLASKQ SPECENFLDV GLGRECTSKQ GVLKRESGSD
SDLFHSPSDD MDSIIFPKPE EEHLACDITG SSSSTDDTAS LDRHSSHGSD VSLSQILKPN
RSRDRQSLDG FYSHGMGAEG RESESEPADP GDVEEEEMDS ITEVPANCSV LRSSMRSLSP
FRRHSWGPGK NAASDAEMNH RSSMRVLGDV VRRPPIHRRS FSLEGLTGGA GVGNKPSSSL
EVSSANAEEL RHPFSGEERV DSLVSLSEED LESDQREHRM FDQQICHRSK QQGFNYCTSA
ISSPLTKSIS LMTISHPGLD NSRPFHSTFH NTSANLTESI TEENYNFLPH SPSKKDSEWK
SGTKVSRTFS YIKNKMSSSK KSKEKEKEKD KIKEKEKDSK DKEKDKKTVN GHTFSSIPVV
GPISCSQCMK PFTNKDAYTC ANCSAFVHKG CRESLASCAK VKMKQPKGSL QAHDTSSLPT
VIMRNKPSQP KERPRSAVLL VDETATTPIF ANRRSQQSVS LSKSVSIQNI TGVGNDENMS
NTWKFLSHST DSLNKISKVN ESTESLTDEG VGTDMNEGQL LGDFEIESKQ LEAESWSRII
DSKFLKQQKK DVVKRQEVIY ELMQTEFHHV RTLKIMSGVY SQGMMADLLF EQQMVEKLFP
CLDELISIHS QFFQRILERK KESLVDKSEK NFLIKRIGDV LVNQFSGENA ERLKKTYGKF
CGQHNQSVNY FKDLYAKDKR FQAFVKKKMS SSVVRRLGIP ECILLVTQRI TKYPVLFQRI
LQCTKDNEVE QEDLAQSLSL VKDVIGAVDS KVASYEKKVR LNEIYTKTDS KSIMRMKSGQ
MFAKEDLKRK KLVRDGSVFL KNAAGRLKEV QAVLLTDILV FLQEKDQKYI FASLDQKSTV
ISLKKLIVRE VAHEEKGLFL ISMGMTDPEM VEVHASSKEE RNSWIQIIQD TINTLNRDED
EGIPSENEEE KKMLDTRARE LKEQLHQKDQ KILLLLEEKE MIFRDMAECS TPLPEDCSPT
HSPRVLFRSN TEEALKGGPL MKSAINEVEI LQGLVSGNLG GTLGPTVSSP IEQDVVGPVS
LPRRAETFGG FDSHQMNASK GGEKEEGDDG QDLRRTESDS GLKKGGNANL VFMLKRNSEQ
VVQSVVHLYE LLSALQGVVL QQDSYIEDQK LVLSERALTR SLSRPSSLIE QEKQRSLEKQ
RQDLANLQKQ QAQYLEEKRR REREWEARER ELREREALLA QREEEVQQGQ QDLEKEREEL
QQKKGTYQYD LERLRAAQKQ LEREQEQLRR EAERLSQRQT ERDLCQVSHP HTKLMRIPSF
FPSPEEPPSP SAPSIAKSGS LDSELSVSPK RNSISRTHKD KGPFHILSST SQTNKGPEGQ
SQAPASTSAS TRLFGLTKPK EKKEKKKKNK TSRSQPGDGP ASEVSAEGEE IFC
