Reviewed, UniProtKB/Swiss-Prot Q9Y243 (AKT3_HUMAN)

Names and origin

Protein names

Recommended name:
    RAC-gamma serine/threonine-protein kinase
    EC=2.7.11.1
Alternative name(s):
    RAC-PK-gamma
    Protein kinase Akt-3
    Protein kinase B gamma
      Short name=PKB gamma
    STK-2

Gene names

Name:	AKT3
Synonyms:	PKBG

Organism

Homo sapiens (Human) [Complete proteome]

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	IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival. Capable of phosphorylating several known proteins. Truncated isoform 2/PKB gamma 1 without the second serine phosphorylation site could still be stimulated but to a lesser extent.
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.
Subunit structure	Interacts (via PH domain) with TCL1A; this enhances AKT3 phosphorylation and activation. Interacts with TRAF6. Ref.11 Ref.12
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein. Note: Membrane-associated after cell stimulation leading to its translocation.
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	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.10 Ref.13
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.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc signal transduction Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.14 Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC37	Q16543	1	EBI-296115,EBI-295634

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.13
	Modified residue	123	1	Phosphoserine Ref.13
	Modified residue	305	1	Phosphothreonine; by PDPK1 Ref.10
	Modified residue	472	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	452 – 479	28	YDEDG…ASGRE → CQQSDCGMLGNWKK in isoform 2.		VSP_004947
	Natural variant	171	1	G → R in a glioblastoma multiforme sample; somatic mutation. Ref.15		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

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). 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]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
+	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_005456.1. NP_859029.1.
UniGene	Hs.498292
3D structure databases
SMR	Q9Y243. Positions 1-115, 142-476.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y243. 1 interaction.
STRING	Q9Y243.
PTM databases
PhosphoSite	Q9Y243.
Proteomic databases
PRIDE	Q9Y243.
Genome annotation databases
Ensembl	ENST00000263826; ENSP00000263826; ENSG00000117020; Homo sapiens. [Genome view] ENST00000366539; ENSP00000355497; ENSG00000117020; Homo sapiens. [Genome view]
GeneID	10000.
KEGG	hsa:10000.
NMPDR	fig|9606.3.peg.3340.
UCSC	uc001hzz.1. human. uc001iab.1. human.
Organism-specific databases
CTD	10000.
GeneCards	GC01M241718.
H-InvDB	HIX0001744.
HGNC	HGNC:393. AKT3.
HPA	CAB013090. HPA026441.
MIM	611223. gene.
PharmGKB	PA24686.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15723.
HOGENOM	HBG755340.
HOVERGEN	Q9Y243.
InParanoid	Q9Y243.
OMA	IMSDVTI.
OrthoDB	EOG97H886.
PhylomeDB	Q9Y243.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Pathway_Interaction_DB	pi3kciaktpathway. Class I PI3K signaling events mediated by Akt. s1p_s1p3_pathway. S1P3 pathway.
Reactome	REACT_11061. Signalling by NGF. REACT_13698. Regulation of beta-cell development. REACT_14797. Signaling by GPCR. REACT_604. Hemostasis. REACT_6900. Signaling in 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_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. IPR015744. Serine/threonine_Kinase_Rac. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit.
PANTHER	PTHR22985:SF69. Akt. 1 hit.
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]
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 Resources
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:	February 9, 2010
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.