AKT3_HUMAN
ID AKT3_HUMAN Reviewed; 479 AA.
AC Q9Y243; Q0VAA6; Q5VTI1; Q5VTI2; Q96QV3; Q9UFP5;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=RAC-gamma serine/threonine-protein kinase;
DE EC=2.7.11.1;
DE AltName: Full=Protein kinase Akt-3;
DE AltName: Full=Protein kinase B gamma;
DE Short=PKB gamma;
DE AltName: Full=RAC-PK-gamma;
DE AltName: Full=STK-2;
GN Name=AKT3; Synonyms=PKBG;
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], AND MUTAGENESIS.
RX PubMed=10092583; DOI=10.1074/jbc.274.14.9133;
RA Brodbeck D., Cron P., Hemmings B.A.;
RT "A human protein kinase B gamma with regulatory phosphorylation sites in
RT the activation loop and in the C-terminal hydrophobic domain.";
RL J. Biol. Chem. 274:9133-9136(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10208883; DOI=10.1006/bbrc.1999.0559;
RA Nakatani K., Sakaue H., Thompson D.A., Weigel R.J., Roth R.A.;
RT "Identification of a human Akt3 (protein kinase B gamma) which contains the
RT regulatory serine phosphorylation site.";
RL Biochem. Biophys. Res. Commun. 257:906-910(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=10491192; DOI=10.1046/j.1432-1327.1999.00774.x;
RA Masure S., Haefner B., Wesselink J.-J., Hoefnagel E., Mortier E.,
RA Verhasselt P., Tuytelaars A., Gordon R., Richardson A.;
RT "Molecular cloning, expression and characterization of the human
RT serine/threonine kinase Akt-3.";
RL Eur. J. Biochem. 265:353-360(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Li X., Yu L., Huang H., Zhang M., Zhao Y., Zhao S.;
RT "Cloning of a novel human cDNA, STK-2, which encodes a rat serine-threonine
RT protein kinase (STK) homolog.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND MUTAGENESIS OF THR-305
RP AND THR-447.
RX PubMed=11387345; DOI=10.1074/jbc.m104633200;
RA Brodbeck D., Hill M.M., Hemmings B.A.;
RT "Two splice variants of PKB gamma have different regulatory capacity
RT depending on the presence or absence of the regulatory phosphorylation site
RT Ser-472 in the C-terminal hydrophobic domain.";
RL J. Biol. Chem. 276:29550-29558(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [10]
RP CHARACTERIZATION, AND PHOSPHORYLATION AT THR-305 BY PDPK1.
RX PubMed=9512493; DOI=10.1042/bj3310299;
RA Walker K.S., Deak M., Paterson A., Hudson K., Cohen P., Alessi D.R.;
RT "Activation of protein kinase B beta and gamma isoforms by insulin in vivo
RT and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison
RT with protein kinase B alpha.";
RL Biochem. J. 331:299-308(1998).
RN [11]
RP PHOSPHORYLATION AT SER-472.
RX PubMed=12162751; DOI=10.1021/bi026065r;
RA Hodgkinson C.P., Sale E.M., Sale G.J.;
RT "Characterization of PDK2 activity against protein kinase B gamma.";
RL Biochemistry 41:10351-10359(2002).
RN [12]
RP INTERACTION WITH TCL1A.
RX PubMed=11707444; DOI=10.1074/jbc.m107069200;
RA Laine J., Kuenstle G., Obata T., Noguchi M.;
RT "Differential regulation of Akt kinase isoforms by the members of the TCL1
RT oncogene family.";
RL J. Biol. Chem. 277:3743-3751(2002).
RN [13]
RP INTERACTION WITH TCL1A.
RX PubMed=11839817; DOI=10.1128/mcb.22.5.1513-1525.2002;
RA Kuenstle G., Laine J., Pierron G., Kagami S., Nakajima H., Hoh F.,
RA Roumestand C., Stern M.H., Noguchi M.;
RT "Identification of Akt association and oligomerization domains of the Akt
RT kinase coactivator TCL1.";
RL Mol. Cell. Biol. 22:1513-1525(2002).
RN [14]
RP INVOLVEMENT IN TUMORS.
RX PubMed=15466193; DOI=10.1158/0008-5472.can-04-1399;
RA Stahl J.M., Sharma A., Cheung M., Zimmerman M., Cheng J.Q., Bosenberg M.W.,
RA Kester M., Sandirasegarane L., Robertson G.P.;
RT "Deregulated Akt3 activity promotes development of malignant melanoma.";
RL Cancer Res. 64:7002-7010(2004).
RN [15]
RP INVOLVEMENT IN CANCER.
RX PubMed=17178867; DOI=10.1158/0008-5472.can-06-1968;
RA Cristiano B.E., Chan J.C., Hannan K.M., Lundie N.A., Marmy-Conus N.J.,
RA Campbell I.G., Phillips W.A., Robbie M., Hannan R.D., Pearson R.B.;
RT "A specific role for AKT3 in the genesis of ovarian cancer through
RT modulation of G(2)-M phase transition.";
RL Cancer Res. 66:11718-11725(2006).
RN [16]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16540465; DOI=10.1074/jbc.m601384200;
RA Zhang X., Zhang S., Yamane H., Wahl R., Ali A., Lofgren J.A., Kendall R.L.;
RT "Kinetic mechanism of AKT/PKB enzyme family.";
RL J. Biol. Chem. 281:13949-13956(2006).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [18]
RP FUNCTION.
RX PubMed=18524868; DOI=10.1096/fj.08-106468;
RA Wright G.L., Maroulakou I.G., Eldridge J., Liby T.L., Sridharan V.,
RA Tsichlis P.N., Muise-Helmericks R.C.;
RT "VEGF stimulation of mitochondrial biogenesis: requirement of AKT3
RT kinase.";
RL FASEB J. 22:3264-3275(2008).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [20]
RP UBIQUITINATION BY TTC3.
RX PubMed=20059950; DOI=10.1016/j.devcel.2009.09.007;
RA Suizu F., Hiramuki Y., Okumura F., Matsuda M., Okumura A.J., Hirata N.,
RA Narita M., Kohno T., Yokota J., Bohgaki M., Obuse C., Hatakeyama S.,
RA Obata T., Noguchi M.;
RT "The E3 ligase TTC3 facilitates ubiquitination and degradation of
RT phosphorylated Akt.";
RL Dev. Cell 17:800-810(2009).
RN [21]
RP INTERACTION WITH TRAF6.
RX PubMed=19713527; DOI=10.1126/science.1175065;
RA Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B.,
RA Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K.;
RT "The E3 ligase TRAF6 regulates Akt ubiquitination and activation.";
RL Science 325:1134-1138(2009).
RN [22]
RP SUBCELLULAR LOCATION.
RX PubMed=20018949; DOI=10.1152/ajpcell.00375.2009;
RA Santi S.A., Lee H.;
RT "The Akt isoforms are present at distinct subcellular locations.";
RL Am. J. Physiol. 298:C580-C591(2010).
RN [23]
RP INVOLVEMENT IN TUMORS.
RX PubMed=20167810; DOI=10.1093/neuonc/nop026;
RA Mure H., Matsuzaki K., Kitazato K.T., Mizobuchi Y., Kuwayama K., Kageji T.,
RA Nagahiro S.;
RT "Akt2 and Akt3 play a pivotal role in malignant gliomas.";
RL Neuro-oncol. 12:221-232(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.
RX PubMed=21191416; DOI=10.1038/jid.2010.361;
RA Moriya C., Jinnin M., Yamane K., Maruo K., Muchemwa F.C., Igata T.,
RA Makino T., Fukushima S., Ihn H.;
RT "Expression of matrix metalloproteinase-13 is controlled by IL-13 via
RT PI3K/Akt3 and PKC-delta in normal human dermal fibroblasts.";
RL J. Invest. Dermatol. 131:655-661(2011).
RN [26]
RP REVIEW ON FUNCTION.
RX PubMed=21620960; DOI=10.1016/j.cellsig.2011.05.004;
RA Hers I., Vincent E.E., Tavare J.M.;
RT "Akt signalling in health and disease.";
RL Cell. Signal. 23:1515-1527(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-447, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE 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 [28]
RP X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) OF 1-118.
RA Vollmar M., Wang J., Zhang Y., Elkins J.M., Burgess-Brown N., Chaikuad A.,
RA Pike A.C.W., Von Delft F., Bountra C., Arrowsmith C.H., Weigelt J.,
RA Edwards A., Knapp S.;
RT "The crystal structure of the PH domain of human Akt3 protein kinase.";
RL Submitted (DEC-2009) to the PDB data bank.
RN [29]
RP VARIANT [LARGE SCALE ANALYSIS] ARG-171.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [30]
RP VARIANT MELANOMA LYS-17, AND CHARACTERIZATION OF VARIANT MELANOMA LYS-17.
RX PubMed=18813315; DOI=10.1038/sj.bjc.6604637;
RA Davies M.A., Stemke-Hale K., Tellez C., Calderone T.L., Deng W.,
RA Prieto V.G., Lazar A.J., Gershenwald J.E., Mills G.B.;
RT "A novel AKT3 mutation in melanoma tumours and cell lines.";
RL Br. J. Cancer 99:1265-1268(2008).
RN [31]
RP VARIANTS MPPH2 SER-229 AND TRP-465.
RX PubMed=22729224; DOI=10.1038/ng.2331;
RA Riviere J.B., Mirzaa G.M., O'Roak B.J., Beddaoui M., Alcantara D.,
RA Conway R.L., St-Onge J., Schwartzentruber J.A., Gripp K.W., Nikkel S.M.,
RA Worthylake T., Sullivan C.T., Ward T.R., Butler H.E., Kramer N.A.,
RA Albrecht B., Armour C.M., Armstrong L., Caluseriu O., Cytrynbaum C.,
RA Drolet B.A., Innes A.M., Lauzon J.L., Lin A.E., Mancini G.M.,
RA Meschino W.S., Reggin J.D., Saggar A.K., Lerman-Sagie T., Uyanik G.,
RA Weksberg R., Zirn B., Beaulieu C.L., Majewski J., Bulman D.E.,
RA O'Driscoll M., Shendure J., Graham J.M. Jr., Boycott K.M., Dobyns W.B.;
RT "De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA
RT cause a spectrum of related megalencephaly syndromes.";
RL Nat. Genet. 44:934-940(2012).
RN [32]
RP VARIANT MPPH2 LYS-17.
RX PubMed=22729223; DOI=10.1038/ng.2329;
RA Lee J.H., Huynh M., Silhavy J.L., Kim S., Dixon-Salazar T., Heiberg A.,
RA Scott E., Bafna V., Hill K.J., Collazo A., Funari V., Russ C.,
RA Gabriel S.B., Mathern G.W., Gleeson J.G.;
RT "De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway
RT cause hemimegalencephaly.";
RL Nat. Genet. 44:941-945(2012).
RN [33]
RP VARIANT MPPH2 LYS-17.
RX PubMed=22500628; DOI=10.1016/j.neuron.2012.03.010;
RA Poduri A., Evrony G.D., Cai X., Elhosary P.C., Beroukhim R., Lehtinen M.K.,
RA Hills L.B., Heinzen E.L., Hill A., Hill R.S., Barry B.J., Bourgeois B.F.,
RA Riviello J.J., Barkovich A.J., Black P.M., Ligon K.L., Walsh C.A.;
RT "Somatic activation of AKT3 causes hemispheric developmental brain
RT malformations.";
RL Neuron 74:41-48(2012).
RN [34]
RP VARIANT MPPH2 SER-229.
RX PubMed=23745724; DOI=10.1111/cge.12188;
RA Nakamura K., Kato M., Tohyama J., Shiohama T., Hayasaka K., Nishiyama K.,
RA Kodera H., Nakashima M., Tsurusaki Y., Miyake N., Matsumoto N., Saitsu H.;
RT "AKT3 and PIK3R2 mutations in two patients with megalencephaly-related
RT syndromes: MCAP and MPPH.";
RL Clin. Genet. 85:396-398(2014).
CC -!- FUNCTION: AKT3 is one of 3 closely related serine/threonine-protein
CC kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate
CC many processes including metabolism, proliferation, cell survival,
CC growth and angiogenesis. This is mediated through serine and/or
CC threonine phosphorylation of a range of downstream substrates. Over 100
CC substrate candidates have been reported so far, but for most of them,
CC no isoform specificity has been reported. AKT3 is the least studied AKT
CC isoform. It plays an important role in brain development and is crucial
CC for the viability of malignant glioma cells. AKT3 isoform may also be
CC the key molecule in up-regulation and down-regulation of MMP13 via
CC IL13. Required for the coordination of mitochondrial biogenesis with
CC growth factor-induced increases in cellular energy demands. Down-
CC regulation by RNA interference reduces the expression of the
CC phosphorylated form of BAD, resulting in the induction of caspase-
CC dependent apoptosis. {ECO:0000269|PubMed:18524868,
CC ECO:0000269|PubMed:21191416}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- ACTIVITY REGULATION: Two specific sites, one in the kinase domain (Thr-
CC 305) and the other in the C-terminal regulatory region (Ser-472), need
CC to be phosphorylated for its full activation (By similarity). IGF-1
CC leads to the activation of AKT3, which may play a role in regulating
CC cell survival. {ECO:0000250}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=87.9 uM for ATP (for purified and in vitro activated AKT3)
CC {ECO:0000269|PubMed:16540465};
CC KM=12.4 uM for peptide substrate (for purified and in vitro activated
CC AKT3) {ECO:0000269|PubMed:16540465};
CC KM=118.7 uM for ATP (for recombinant myristoylated AKT3 expressed and
CC immunoprecipitated from Rat-1 cells) {ECO:0000269|PubMed:16540465};
CC KM=2.3 uM for peptide substrate (for recombinant myristoylated AKT3
CC expressed and immunoprecipitated from Rat-1 cells)
CC {ECO:0000269|PubMed:16540465};
CC -!- SUBUNIT: Interacts (via PH domain) with TCL1A; this enhances AKT3
CC phosphorylation and activation. Interacts with TRAF6. Interacts with
CC KCTD20 (By similarity). Interacts with BTBD10 (By similarity).
CC {ECO:0000250|UniProtKB:Q9WUA6, ECO:0000269|PubMed:11707444,
CC ECO:0000269|PubMed:11839817, ECO:0000269|PubMed:19713527}.
CC -!- INTERACTION:
CC Q9Y243; P42574: CASP3; NbExp=2; IntAct=EBI-296115, EBI-524064;
CC Q9Y243; Q16543: CDC37; NbExp=2; IntAct=EBI-296115, EBI-295634;
CC Q9Y243; P53804: TTC3; NbExp=2; IntAct=EBI-296115, EBI-2681313;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20018949}. Cytoplasm
CC {ECO:0000269|PubMed:20018949}. Membrane {ECO:0000269|PubMed:20018949};
CC Peripheral membrane protein {ECO:0000269|PubMed:20018949}.
CC Note=Membrane-associated after cell stimulation leading to its
CC translocation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PKB gamma;
CC IsoId=Q9Y243-1; Sequence=Displayed;
CC Name=2; Synonyms=PKB gamma 1;
CC IsoId=Q9Y243-2; Sequence=VSP_004947;
CC -!- TISSUE SPECIFICITY: In adult tissues, it is highly expressed in brain,
CC lung and kidney, but weakly in heart, testis and liver. In fetal
CC tissues, it is highly expressed in heart, liver and brain and not at
CC all in kidney.
CC -!- DOMAIN: Binding of the PH domain to the phosphatidylinositol 3-kinase
CC alpha (PI(3)K) results in its targeting to the plasma membrane.
CC -!- PTM: Phosphorylation on Thr-305 and Ser-472 is required for full
CC activity. {ECO:0000250}.
CC -!- PTM: Ubiquitinated. When fully phosphorylated and translocated into the
CC nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3,
CC leading to its degradation by the proteasome.
CC {ECO:0000269|PubMed:12162751, ECO:0000269|PubMed:20059950,
CC ECO:0000269|PubMed:9512493}.
CC -!- PTM: O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating
CC phosphorylation at Thr-305 via disrupting the interaction between AKT
CC and PDK1. {ECO:0000250}.
CC -!- DISEASE: Note=AKT3 is a key modulator of several tumors like melanoma,
CC glioma and ovarian cancer. Active AKT3 increases progressively during
CC melanoma tumor progression with highest levels present in advanced-
CC stage metastatic melanomas. Promotes melanoma tumorigenesis by
CC decreasing apoptosis. Plays a key role in the genesis of ovarian
CC cancers through modulation of G2/M phase transition. With AKT2, plays a
CC pivotal role in the biology of glioblastoma.
CC -!- DISEASE: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus
CC syndrome 2 (MPPH2) [MIM:615937]: A syndrome characterized by
CC megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also
CC be seen. There is considerable phenotypic similarity between this
CC disorder and the megalencephaly-capillary malformation syndrome.
CC {ECO:0000269|PubMed:22500628, ECO:0000269|PubMed:22729223,
CC ECO:0000269|PubMed:22729224, ECO:0000269|PubMed:23745724}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. RAC subfamily. {ECO:0000305}.
CC -!- CAUTION: In light of strong homologies in the primary amino acid
CC sequence, the 3 AKT kinases were long surmised to play redundant and
CC overlapping roles. More recent studies has brought into question the
CC redundancy within AKT kinase isoforms and instead pointed to isoform
CC specific functions in different cellular events and diseases. AKT1 is
CC more specifically involved in cellular survival pathways, by inhibiting
CC apoptotic processes; whereas AKT2 is more specific for the insulin
CC receptor signaling pathway. Moreover, while AKT1 and AKT2 are often
CC implicated in many aspects of cellular transformation, the 2 isoforms
CC act in a complementary opposing manner. The role of AKT3 is less clear,
CC though it appears to be predominantly expressed in brain.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/AKT3ID615ch1q44.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF124141; AAD29089.1; -; mRNA.
DR EMBL; AF135794; AAD24196.1; -; mRNA.
DR EMBL; AF085234; AAL40392.1; -; mRNA.
DR EMBL; AJ245709; CAB53537.1; -; mRNA.
DR EMBL; AL117525; CAB55977.1; ALT_TERM; mRNA.
DR EMBL; AY005799; AAF91073.1; -; mRNA.
DR EMBL; AC096539; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591721; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL592151; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL662889; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471148; EAW77093.1; -; Genomic_DNA.
DR EMBL; CH471148; EAW77094.1; -; Genomic_DNA.
DR EMBL; BC121154; AAI21155.1; -; mRNA.
DR CCDS; CCDS31076.1; -. [Q9Y243-2]
DR CCDS; CCDS31077.1; -. [Q9Y243-1]
DR PIR; A59380; A59380.
DR PIR; T17287; T17287.
DR RefSeq; NP_001193658.1; NM_001206729.1. [Q9Y243-2]
DR RefSeq; NP_005456.1; NM_005465.4. [Q9Y243-1]
DR RefSeq; NP_859029.1; NM_181690.2. [Q9Y243-2]
DR RefSeq; XP_005273051.1; XM_005272994.4.
DR RefSeq; XP_005273052.1; XM_005272995.2.
DR PDB; 2X18; X-ray; 1.46 A; A/B/C/D/E/F/G/H=1-118.
DR PDBsum; 2X18; -.
DR AlphaFoldDB; Q9Y243; -.
DR SMR; Q9Y243; -.
DR BioGRID; 115318; 59.
DR DIP; DIP-32584N; -.
DR IntAct; Q9Y243; 47.
DR MINT; Q9Y243; -.
DR STRING; 9606.ENSP00000263826; -.
DR BindingDB; Q9Y243; -.
DR ChEMBL; CHEMBL4816; -.
DR DrugCentral; Q9Y243; -.
DR GuidetoPHARMACOLOGY; 2286; -.
DR GlyGen; Q9Y243; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y243; -.
DR PhosphoSitePlus; Q9Y243; -.
DR BioMuta; AKT3; -.
DR DMDM; 12643943; -.
DR EPD; Q9Y243; -.
DR jPOST; Q9Y243; -.
DR MassIVE; Q9Y243; -.
DR MaxQB; Q9Y243; -.
DR PaxDb; Q9Y243; -.
DR PeptideAtlas; Q9Y243; -.
DR PRIDE; Q9Y243; -.
DR ProteomicsDB; 85641; -. [Q9Y243-1]
DR ProteomicsDB; 85642; -. [Q9Y243-2]
DR ABCD; Q9Y243; 3 sequenced antibodies.
DR Antibodypedia; 3402; 1176 antibodies from 46 providers.
DR CPTC; Q9Y243; 7 antibodies.
DR DNASU; 10000; -.
DR Ensembl; ENST00000263826.12; ENSP00000263826.5; ENSG00000117020.19. [Q9Y243-1]
DR Ensembl; ENST00000336199.9; ENSP00000336943.5; ENSG00000117020.19. [Q9Y243-2]
DR Ensembl; ENST00000366540.5; ENSP00000355498.1; ENSG00000117020.19. [Q9Y243-2]
DR Ensembl; ENST00000613395.4; ENSP00000479922.1; ENSG00000275199.4. [Q9Y243-2]
DR Ensembl; ENST00000619536.4; ENSP00000483054.1; ENSG00000275199.4. [Q9Y243-2]
DR Ensembl; ENST00000621586.3; ENSP00000479081.1; ENSG00000275199.4. [Q9Y243-1]
DR Ensembl; ENST00000673466.1; ENSP00000500582.1; ENSG00000117020.19. [Q9Y243-1]
DR Ensembl; ENST00000680118.1; ENSP00000505276.1; ENSG00000117020.19. [Q9Y243-1]
DR GeneID; 10000; -.
DR KEGG; hsa:10000; -.
DR MANE-Select; ENST00000673466.1; ENSP00000500582.1; NM_005465.7; NP_005456.1.
DR UCSC; uc001hzz.2; human. [Q9Y243-1]
DR CTD; 10000; -.
DR DisGeNET; 10000; -.
DR GeneCards; AKT3; -.
DR GeneReviews; AKT3; -.
DR HGNC; HGNC:393; AKT3.
DR HPA; ENSG00000117020; Tissue enhanced (brain).
DR MalaCards; AKT3; -.
DR MIM; 611223; gene.
DR MIM; 615937; phenotype.
DR neXtProt; NX_Q9Y243; -.
DR OpenTargets; ENSG00000117020; -.
DR Orphanet; 99802; Hemimegalencephaly.
DR Orphanet; 83473; Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome.
DR PharmGKB; PA24686; -.
DR VEuPathDB; HostDB:ENSG00000117020; -.
DR eggNOG; KOG0690; Eukaryota.
DR GeneTree; ENSGT00940000157060; -.
DR HOGENOM; CLU_000288_11_0_1; -.
DR InParanoid; Q9Y243; -.
DR OMA; XLGGGPD; -.
DR OrthoDB; 787710at2759; -.
DR PhylomeDB; Q9Y243; -.
DR TreeFam; TF102004; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q9Y243; -.
DR Reactome; R-HSA-111447; Activation of BAD and translocation to mitochondria.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-1358803; Downregulation of ERBB2:ERBB3 signaling.
DR Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-HSA-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-HSA-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-HSA-211163; AKT-mediated inactivation of FOXO1A.
DR Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-HSA-389513; CTLA4 inhibitory signaling.
DR Reactome; R-HSA-392451; G beta:gamma signalling through PI3Kgamma.
DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer.
DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR Reactome; R-HSA-6804758; Regulation of TP53 Activity through Acetylation.
DR Reactome; R-HSA-6804759; Regulation of TP53 Activity through Association with Co-factors.
DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR Reactome; R-HSA-8941332; RUNX2 regulates genes involved in cell migration.
DR Reactome; R-HSA-8948751; Regulation of PTEN stability and activity.
DR Reactome; R-HSA-9607240; FLT3 Signaling.
DR Reactome; R-HSA-9614399; Regulation of localization of FOXO transcription factors.
DR Reactome; R-HSA-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway.
DR Reactome; R-HSA-9755779; SARS-CoV-2 targets host intracellular signalling and regulatory pathways.
DR SABIO-RK; Q9Y243; -.
DR SignaLink; Q9Y243; -.
DR SIGNOR; Q9Y243; -.
DR BioGRID-ORCS; 10000; 12 hits in 1117 CRISPR screens.
DR ChiTaRS; AKT3; human.
DR GeneWiki; AKT3; -.
DR GenomeRNAi; 10000; -.
DR Pharos; Q9Y243; Tchem.
DR PRO; PR:Q9Y243; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9Y243; protein.
DR Bgee; ENSG00000117020; Expressed in cortical plate and 156 other tissues.
DR ExpressionAtlas; Q9Y243; baseline and differential.
DR Genevisible; Q9Y243; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0048854; P:brain morphogenesis; IEA:Ensembl.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0000002; P:mitochondrial genome maintenance; IMP:UniProtKB.
DR GO; GO:2000773; P:negative regulation of cellular senescence; IMP:BHF-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:1905653; P:positive regulation of artery morphogenesis; IEA:Ensembl.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:BHF-UCL.
DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; IMP:BHF-UCL.
DR GO; GO:0045793; P:positive regulation of cell size; IEA:Ensembl.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:BHF-UCL.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IEA:Ensembl.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IDA:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; IMP:UniProtKB.
DR CDD; cd01241; PH_PKB; 1.
DR CDD; cd05593; STKc_PKB_gamma; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR034675; Akt3.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR039026; PH_PKB.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR039029; RAC_gamma-like.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24351:SF199; PTHR24351:SF199; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW Disease variant; Disulfide bond; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..479
FT /note="RAC-gamma serine/threonine-protein kinase"
FT /id="PRO_0000085611"
FT DOMAIN 5..107
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 148..405
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 406..479
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 458..479
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 271
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 154..162
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 177
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 305
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000269|PubMed:9512493"
FT MOD_RES 447
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 472
FT /note="Phosphoserine; by PKC/PRKCZ"
FT /evidence="ECO:0000269|PubMed:12162751"
FT CARBOHYD 302
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250"
FT CARBOHYD 309
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250"
FT DISULFID 59..76
FT /evidence="ECO:0000250"
FT DISULFID 293..307
FT /evidence="ECO:0000250"
FT VAR_SEQ 452..479
FT /note="YDEDGMDCMDNERRPHFPQFSYSASGRE -> CQQSDCGMLGNWKK (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:11230166,
FT ECO:0000303|PubMed:11387345, ECO:0000303|PubMed:15489334"
FT /id="VSP_004947"
FT VARIANT 17
FT /note="E -> K (in MPPH2 and melanoma; results in activation
FT of AKT; dbSNP:rs397514606)"
FT /evidence="ECO:0000269|PubMed:18813315,
FT ECO:0000269|PubMed:22500628, ECO:0000269|PubMed:22729223"
FT /id="VAR_065830"
FT VARIANT 171
FT /note="G -> R (in a glioblastoma multiforme sample; somatic
FT mutation; dbSNP:rs1402272180)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040358"
FT VARIANT 229
FT /note="N -> S (in MPPH2; dbSNP:rs397514605)"
FT /evidence="ECO:0000269|PubMed:22729224,
FT ECO:0000269|PubMed:23745724"
FT /id="VAR_069260"
FT VARIANT 465
FT /note="R -> W (in MPPH2; disease phenotype overlaps with
FT megalencephaly-capillary malformation syndrome;
FT dbSNP:rs587776935)"
FT /evidence="ECO:0000269|PubMed:22729224"
FT /id="VAR_069261"
FT MUTAGEN 305
FT /note="T->A: No activation after pervanadate treatment."
FT /evidence="ECO:0000269|PubMed:11387345"
FT MUTAGEN 305
FT /note="T->D: 2-fold increase of phosphorylation steady
FT state level, no activation after pervanadate treatment."
FT /evidence="ECO:0000269|PubMed:11387345"
FT MUTAGEN 447
FT /note="T->A: No effect."
FT /evidence="ECO:0000269|PubMed:11387345"
FT MUTAGEN 447
FT /note="T->D: No effect."
FT /evidence="ECO:0000269|PubMed:11387345"
FT MUTAGEN 472
FT /note="S->A: 67% decrease of activity after pervanadate
FT treatment."
FT /evidence="ECO:0000269|PubMed:10092583"
FT MUTAGEN 472
FT /note="S->D: 1.4-fold increase of phosphorylation steady
FT state level, 50% decrease of activity after pervanadate
FT treatment."
FT /evidence="ECO:0000269|PubMed:10092583"
FT CONFLICT 279
FT /note="L -> R (in Ref. 9; AAI21155)"
FT /evidence="ECO:0000305"
FT STRAND 6..15
FT /evidence="ECO:0007829|PDB:2X18"
FT STRAND 17..30
FT /evidence="ECO:0007829|PDB:2X18"
FT STRAND 33..41
FT /evidence="ECO:0007829|PDB:2X18"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:2X18"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:2X18"
FT STRAND 60..64
FT /evidence="ECO:0007829|PDB:2X18"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:2X18"
FT STRAND 71..75
FT /evidence="ECO:0007829|PDB:2X18"
FT TURN 80..82
FT /evidence="ECO:0007829|PDB:2X18"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:2X18"
FT HELIX 92..113
FT /evidence="ECO:0007829|PDB:2X18"
SQ SEQUENCE 479 AA; 55775 MW; F08BDDE6502E78FB CRC64;
MSDVTIVKEG WVQKRGEYIK NWRPRYFLLK TDGSFIGYKE KPQDVDLPYP LNNFSVAKCQ
LMKTERPKPN TFIIRCLQWT TVIERTFHVD TPEEREEWTE AIQAVADRLQ RQEEERMNCS
PTSQIDNIGE EEMDASTTHH KRKTMNDFDY LKLLGKGTFG KVILVREKAS GKYYAMKILK
KEVIIAKDEV AHTLTESRVL KNTRHPFLTS LKYSFQTKDR LCFVMEYVNG GELFFHLSRE
RVFSEDRTRF YGAEIVSALD YLHSGKIVYR DLKLENLMLD KDGHIKITDF GLCKEGITDA
ATMKTFCGTP EYLAPEVLED NDYGRAVDWW GLGVVMYEMM CGRLPFYNQD HEKLFELILM
EDIKFPRTLS SDAKSLLSGL LIKDPNKRLG GGPDDAKEIM RHSFFSGVNW QDVYDKKLVP
PFKPQVTSET DTRYFDEEFT AQTITITPPE KYDEDGMDCM DNERRPHFPQ FSYSASGRE
