Q9Y243 (AKT3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
RAC-gamma serine/threonine-protein kinase
EC=2.7.11.1

Alternative name(s):
Protein kinase Akt-3
Protein kinase B gamma
Short name=PKB gamma
RAC-PK-gamma
STK-2

Gene names

Name:	AKT3
Synonyms:	PKBG

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	479 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. Ref.18 Ref.23
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Two specific sites, one in the kinase domain (Thr-305) and the other in the C-terminal regulatory region (Ser-472), need to be phosphorylated for its full activation By similarity. IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival.
Subunit structure	Interacts (via PH domain) with TCL1A; this enhances AKT3 phosphorylation and activation. Interacts with TRAF6. Ref.12 Ref.13 Ref.20
Subcellular location	Nucleus. Cytoplasm. Membrane; Peripheral membrane protein. Note: Membrane-associated after cell stimulation leading to its translocation. Ref.21
Tissue specificity	In adult tissues, it is highly expressed in brain, lung and kidney, but weakly in heart, testis and liver. In fetal tissues, it is highly expressed in heart, liver and brain and not at all in kidney.
Domain	Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI3K) results in its targeting to the plasma membrane.
Post-translational modification	Phosphorylation on Thr-305 and Ser-472 is required for full activity By similarity. Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.10 Ref.11 Ref.17 Ubiquitinated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome. Ref.10 Ref.11 Ref.17
Involvement in disease	Note=AKT3 is a key modulator of several tumors like melanoma, glioma and ovarian cancer. Active AKT3 increases progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Promotes melanoma tumorigenesis by decreasing apoptosis. Plays a key role in the genesis of ovarian cancers through modulation of G2/M phase transition. With AKT2, plays a pivotal role in the biology of glioblastoma.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 PH domain. Contains 1 protein kinase domain.
Caution	In light of strong homologies in the primary amino acid sequence, the 3 AKT kinases were long surmised to play redundant and overlapping roles. More recent studies has brought into question the redundancy within AKT kinase isoforms and instead pointed to isoform specific functions in different cellular events and diseases. AKT1 is more specifically involved in cellular survival pathways, by inhibiting apoptotic processes; whereas AKT2 is more specific for the insulin receptor signaling pathway. Moreover, while AKT1 and AKT2 are often implicated in many aspects of cellular transformation, the 2 isoforms act in a complementary opposing manner. The role of AKT3 is less clear, though it appears to be predominantly expressed in brain.
Biophysicochemical properties	Kinetic parameters: KM=87.9 µM for ATP (for purified and in vitro activated AKT3) Ref.16 KM=12.4 µM for peptide substrate (for purified and in vitro activated AKT3) KM=118.7 µM for ATP (for recombinant myristoylated AKT3 expressed and immunoprecipitated from Rat-1 cells) KM=2.3 µM for peptide substrate (for recombinant myristoylated AKT3 expressed and immunoprecipitated from Rat-1 cells)

Ontologies

Keywords
Cellular component	Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Disulfide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	mitochondrial genome maintenance Inferred from mutant phenotype Ref.18. Source: UniProtKB signal transduction Inferred from mutant phenotype Ref.18. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular function	ATP binding Inferred from direct assay Ref.16. Source: UniProtKB protein binding Inferred from physical interaction Ref.20Ref.19. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.16. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y243-1)

Also known as: PKB gamma;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9Y243-2)

Also known as: PKB gamma 1;

The sequence of this isoform differs from the canonical sequence as follows:
     452-479: YDEDGMDCMDNERRPHFPQFSYSASGRE → CQQSDCGMLGNWKK

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 479

479

RAC-gamma serine/threonine-protein kinase

PRO_0000085611

Regions

Domain

5 – 107

103

PH

Domain

148 – 405

258

Protein kinase

Domain

406 – 479

74

AGC-kinase C-terminal

Nucleotide binding

154 – 162

9

ATP By similarity

Sites

Active site

271

1

Proton acceptor By similarity

Binding site

177

1

ATP By similarity

Amino acid modifications

Modified residue

120

1

Phosphoserine Ref.17

Modified residue

123

1

Phosphoserine Ref.17

Modified residue

305

1

Phosphothreonine; by PDPK1 Ref.10

Modified residue

472

1

Phosphoserine; by PKC/PRKCZ Ref.11

Disulfide bond

59 ↔ 76

By similarity

Disulfide bond

293 ↔ 307

By similarity

Natural variations

Alternative sequence

452 – 479

28

YDEDG…ASGRE → CQQSDCGMLGNWKK in isoform 2.

VSP_004947

Natural variant

17

1

E → K in melanoma; results in activation of AKT. Ref.27

VAR_065830

Natural variant

171

1

G → R in a glioblastoma multiforme sample; somatic mutation. Ref.26

VAR_040358

Experimental info

Mutagenesis

305

1

T → A: No activation after pervanadate treatment. Ref.6

Mutagenesis

305

1

T → D: 2-fold increase of phosphorylation steady state level, no activation after pervanadate treatment. Ref.6

Mutagenesis

447

1

T → A: No effect. Ref.6

Mutagenesis

447

1

T → D: No effect. Ref.6

Mutagenesis

472

1

S → A: 67% decrease of activity after pervanadate treatment.

Mutagenesis

472

1

S → D: 1.4-fold increase of phosphorylation steady state level, 50% decrease of activity after pervanadate treatment.

Sequence conflict

279

1

L → R in AAI21155. Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

479

Helix Strand Turn

Details...

Beta strand

6 – 8

3

Beta strand

12 – 14

3

Beta strand

19 – 21

3

Beta strand

23 – 25

3

Beta strand

28 – 30

3

Helix

44 – 46

3

Beta strand

60 – 64

5

Beta strand

66 – 68

3

Beta strand

71 – 75

5

Turn

80 – 82

3

Beta strand

84 – 88

5

Helix

92 – 113

22

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PKB gamma) [UniParc]. Last modified November 1, 1999. Version 1. Checksum: F08BDDE6502E78FB	FASTA	479	55,775
	10 20 30 40 50 60 MSDVTIVKEG WVQKRGEYIK NWRPRYFLLK TDGSFIGYKE KPQDVDLPYP LNNFSVAKCQ 70 80 90 100 110 120 LMKTERPKPN TFIIRCLQWT TVIERTFHVD TPEEREEWTE AIQAVADRLQ RQEEERMNCS 130 140 150 160 170 180 PTSQIDNIGE EEMDASTTHH KRKTMNDFDY LKLLGKGTFG KVILVREKAS GKYYAMKILK 190 200 210 220 230 240 KEVIIAKDEV AHTLTESRVL KNTRHPFLTS LKYSFQTKDR LCFVMEYVNG GELFFHLSRE 250 260 270 280 290 300 RVFSEDRTRF YGAEIVSALD YLHSGKIVYR DLKLENLMLD KDGHIKITDF GLCKEGITDA 310 320 330 340 350 360 ATMKTFCGTP EYLAPEVLED NDYGRAVDWW GLGVVMYEMM CGRLPFYNQD HEKLFELILM 370 380 390 400 410 420 EDIKFPRTLS SDAKSLLSGL LIKDPNKRLG GGPDDAKEIM RHSFFSGVNW QDVYDKKLVP 430 440 450 460 470 PFKPQVTSET DTRYFDEEFT AQTITITPPE KYDEDGMDCM DNERRPHFPQ FSYSASGRE
	Isoform 2 (PKB gamma 1) [UniParc]. Checksum: 592EF88B6937D1E0	FASTA	465	54,032
	10 20 30 40 50 60 MSDVTIVKEG WVQKRGEYIK NWRPRYFLLK TDGSFIGYKE KPQDVDLPYP LNNFSVAKCQ 70 80 90 100 110 120 LMKTERPKPN TFIIRCLQWT TVIERTFHVD TPEEREEWTE AIQAVADRLQ RQEEERMNCS 130 140 150 160 170 180 PTSQIDNIGE EEMDASTTHH KRKTMNDFDY LKLLGKGTFG KVILVREKAS GKYYAMKILK 190 200 210 220 230 240 KEVIIAKDEV AHTLTESRVL KNTRHPFLTS LKYSFQTKDR LCFVMEYVNG GELFFHLSRE 250 260 270 280 290 300 RVFSEDRTRF YGAEIVSALD YLHSGKIVYR DLKLENLMLD KDGHIKITDF GLCKEGITDA 310 320 330 340 350 360 ATMKTFCGTP EYLAPEVLED NDYGRAVDWW GLGVVMYEMM CGRLPFYNQD HEKLFELILM 370 380 390 400 410 420 EDIKFPRTLS SDAKSLLSGL LIKDPNKRLG GGPDDAKEIM RHSFFSGVNW QDVYDKKLVP 430 440 450 460 PFKPQVTSET DTRYFDEEFT AQTITITPPE KCQQSDCGML GNWKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human protein kinase B gamma with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain." Brodbeck D., Cron P., Hemmings B.A. J. Biol. Chem. 274:9133-9136(1999) [PubMed: 10092583] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS.
[2]	"Identification of a human Akt3 (protein kinase B gamma) which contains the regulatory serine phosphorylation site." Nakatani K., Sakaue H., Thompson D.A., Weigel R.J., Roth R.A. Biochem. Biophys. Res. Commun. 257:906-910(1999) [PubMed: 10208883] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3." Masure S., Haefner B., Wesselink J.-J., Hoefnagel E., Mortier E., Verhasselt P., Tuytelaars A., Gordon R., Richardson A. Eur. J. Biochem. 265:353-360(1999) [PubMed: 10491192] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[4]	"Cloning of a novel human cDNA, STK-2, which encodes a rat serine-threonine protein kinase (STK) homolog." Li X., Yu L., Huang H., Zhang M., Zhao Y., Zhao S. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[6]	"Two splice variants of PKB gamma have different regulatory capacity depending on the presence or absence of the regulatory phosphorylation site Ser-472 in the C-terminal hydrophobic domain." Brodbeck D., Hill M.M., Hemmings B.A. J. Biol. Chem. 276:29550-29558(2001) [PubMed: 11387345] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), MUTAGENESIS OF THR-305 AND THR-447.
[7]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[10]	"Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha." Walker K.S., Deak M., Paterson A., Hudson K., Cohen P., Alessi D.R. Biochem. J. 331:299-308(1998) [PubMed: 9512493] [Abstract] Cited for: CHARACTERIZATION, PHOSPHORYLATION AT THR-305 BY PDPK1.
[11]	"Characterization of PDK2 activity against protein kinase B gamma." Hodgkinson C.P., Sale E.M., Sale G.J. Biochemistry 41:10351-10359(2002) [PubMed: 12162751] [Abstract] Cited for: PHOSPHORYLATION AT SER-472.
[12]	"Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family." Laine J., Kuenstle G., Obata T., Noguchi M. J. Biol. Chem. 277:3743-3751(2002) [PubMed: 11707444] [Abstract] Cited for: INTERACTION WITH TCL1A.
[13]	"Identification of Akt association and oligomerization domains of the Akt kinase coactivator TCL1." Kuenstle G., Laine J., Pierron G., Kagami S., Nakajima H., Hoh F., Roumestand C., Stern M.H., Noguchi M. Mol. Cell. Biol. 22:1513-1525(2002) [PubMed: 11839817] [Abstract] Cited for: INTERACTION WITH TCL1A.
[14]	"Deregulated Akt3 activity promotes development of malignant melanoma." Stahl J.M., Sharma A., Cheung M., Zimmerman M., Cheng J.Q., Bosenberg M.W., Kester M., Sandirasegarane L., Robertson G.P. Cancer Res. 64:7002-7010(2004) [PubMed: 15466193] [Abstract] Cited for: INVOLVEMENT IN TUMORS.
[15]	"A specific role for AKT3 in the genesis of ovarian cancer through modulation of G(2)-M phase transition." Cristiano B.E., Chan J.C., Hannan K.M., Lundie N.A., Marmy-Conus N.J., Campbell I.G., Phillips W.A., Robbie M., Hannan R.D., Pearson R.B. Cancer Res. 66:11718-11725(2006) [PubMed: 17178867] [Abstract] Cited for: INVOLVEMENT IN TUMORS.
[16]	"Kinetic mechanism of AKT/PKB enzyme family." Zhang X., Zhang S., Yamane H., Wahl R., Ali A., Lofgren J.A., Kendall R.L. J. Biol. Chem. 281:13949-13956(2006) [PubMed: 16540465] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[17]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120 AND SER-123, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[18]	"VEGF stimulation of mitochondrial biogenesis: requirement of AKT3 kinase." Wright G.L., Maroulakou I.G., Eldridge J., Liby T.L., Sridharan V., Tsichlis P.N., Muise-Helmericks R.C. FASEB J. 22:3264-3275(2008) [PubMed: 18524868] [Abstract] Cited for: FUNCTION.
[19]	"The E3 ligase TTC3 facilitates ubiquitination and degradation of phosphorylated Akt." Suizu F., Hiramuki Y., Okumura F., Matsuda M., Okumura A.J., Hirata N., Narita M., Kohno T., Yokota J., Bohgaki M., Obuse C., Hatakeyama S., Obata T., Noguchi M. Dev. Cell 17:800-810(2009) [PubMed: 20059950] [Abstract] Cited for: UBIQUITINATION BY TTC3.
[20]	"The E3 ligase TRAF6 regulates Akt ubiquitination and activation." Yang W.-L., Wang J., Chan C.-H., Lee S.-W., Campos A.D., Lamothe B., Hur L., Grabiner B.C., Lin X., Darnay B.G., Lin H.-K. Science 325:1134-1138(2009) [PubMed: 19713527] [Abstract] Cited for: INTERACTION WITH TRAF6.
[21]	"The Akt isoforms are present at distinct subcellular locations." Santi S.A., Lee H. Am. J. Physiol. 298:C580-C591(2010) [PubMed: 20018949] [Abstract] Cited for: SUBCELLULAR LOCATION.
[22]	"Akt2 and Akt3 play a pivotal role in malignant gliomas." Mure H., Matsuzaki K., Kitazato K.T., Mizobuchi Y., Kuwayama K., Kageji T., Nagahiro S. Neuro-oncol. 12:221-232(2010) [PubMed: 20167810] [Abstract] Cited for: INVOLVEMENT IN TUMORS.
[23]	"Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-delta in normal human dermal fibroblasts." Moriya C., Jinnin M., Yamane K., Maruo K., Muchemwa F.C., Igata T., Makino T., Fukushima S., Ihn H. J. Invest. Dermatol. 131:655-661(2011) [PubMed: 21191416] [Abstract] Cited for: FUNCTION.
[24]	"Akt signalling in health and disease." Hers I., Vincent E.E., Tavare J.M. Cell. Signal. 23:1515-1527(2011) [PubMed: 21620960] [Abstract] Cited for: REVIEW ON FUNCTION.
[25]	"The crystal structure of the Ph domain of human Akt3 protein kinase." Vollmar M., Wang J., Zhang Y., Elkins J.M., Burgess-Brown N., Chaikuad A., Pike A.C.W., Von Delft F., Bountra C., Arrowsmith C.H., Weigelt J., Edwards A., Knapp S. Submitted (DEC-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.46 ANGSTROMS) OF 1-118.
[26]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-171.
[27]	"A novel AKT3 mutation in melanoma tumours and cell lines." Davies M.A., Stemke-Hale K., Tellez C., Calderone T.L., Deng W., Prieto V.G., Lazar A.J., Gershenwald J.E., Mills G.B. Br. J. Cancer 99:1265-1268(2008) [PubMed: 18813315] [Abstract] Cited for: VARIANT MELANOMA LYS-17, CHARACTERIZATION OF VARIANT MELANOMA LYS-17.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF124141 mRNA. Translation: AAD29089.1.
AF135794 mRNA. Translation: AAD24196.1.
AF085234 mRNA. Translation: AAL40392.1.
AJ245709 mRNA. Translation: CAB53537.1.
AL117525 mRNA. Translation: CAB55977.1. Different termination.
AY005799 mRNA. Translation: AAF91073.1.
AL591721 , AC096539, AL592151, AL662889 Genomic DNA. Translation: CAH71866.1.
AL591721 , AC096539, AL592151, AL662889 Genomic DNA. Translation: CAH71867.1.
AL592151 , AC096539, AL591721, AL662889 Genomic DNA. Translation: CAH72891.1.
AL592151 , AC096539, AL591721, AL662889 Genomic DNA. Translation: CAH72892.1.
AL662889 , AC096539, AL591721, AL592151 Genomic DNA. Translation: CAH73072.1.
AL662889 , AC096539, AL591721, AL592151 Genomic DNA. Translation: CAH73073.1.
CH471148 Genomic DNA. Translation: EAW77093.1.
CH471148 Genomic DNA. Translation: EAW77094.1.
BC121154 mRNA. Translation: AAI21155.1.

IPI

IPI00031747.
IPI00219411.

PIR

A59380.
T17287.

RefSeq

NP_001193658.1. NM_001206729.1.
NP_005456.1. NM_005465.4.
NP_859029.1. NM_181690.2.

UniGene

Hs.498292.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2X18	X-ray	1.46	A/B/C/D/E/F/G/H	1-118	[»]

ProteinModelPortal

Q9Y243.

SMR

Q9Y243. Positions 2-476.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y243. 1 interaction.

MINT

MINT-222821.

STRING

Q9Y243.

PTM databases

PhosphoSite

Q9Y243.

Polymorphism databases

DMDM

12643943.

Proteomic databases

PRIDE

Q9Y243.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000263826; ENSP00000263826; ENSG00000117020.
ENST00000366539; ENSP00000355497; ENSG00000117020.

GeneID

10000.

KEGG

hsa:10000.

NMPDR

fig|9606.3.peg.3340.

UCSC

uc001hzz.1. human.
uc001iab.1. human.

Organism-specific databases

CTD

10000.

GeneCards

GC01M243653.

HGNC

HGNC:393. AKT3.

HPA

CAB013090.
HPA026441.

MIM

611223. gene.

neXtProt

NX_Q9Y243.

PharmGKB

PA24686.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15723.

GeneTree

ENSGT00590000082790.

HOGENOM

HBG755340.

HOVERGEN

HBG108317.

InParanoid

Q9Y243.

OMA

IMSDVTI.

OrthoDB

EOG40GCQP.

PhylomeDB

Q9Y243.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Pathway_Interaction_DB

pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.
s1p_s1p3_pathway. S1P3 pathway.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9Y243.

Bgee

Q9Y243.

CleanEx

HS_AKT3.

Genevestigator

Q9Y243.

GermOnline

ENSG00000117020. Homo sapiens.

Family and domain databases

InterPro

IPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR011993. PH_type.
IPR017892. Pkinase_C.
IPR001849. Pleckstrin_homology.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR002290. Ser/Thr_kinase_dom.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.

KO

K04456.

Pfam

PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]

SMART

SM00233. PH. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS51285. AGC_KINASE_CTER. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9Y243.

NextBio

37765.

SOURCE

Search...

Entry information

Entry name

AKT3_HUMAN

Accession

Primary (citable) accession number: Q9Y243
Secondary accession number(s): Q0VAA6 , Q5VTI1, Q5VTI2, Q96QV3, Q9UFP5

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 1, 1999
Last modified:	January 25, 2012
This is version 126 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.