Reviewed, UniProtKB/Swiss-Prot P31751 (AKT2_HUMAN)

Names and origin

Protein names

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

Gene names

Name:

AKT2

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	481 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	General protein kinase capable of phosphorylating several known proteins.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Two specific sites, one in the kinase domain (Thr-309) and the other in the C-terminal regulatory region (Ser-474), need to be phosphorylated for its full activation.
Subunit structure	Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B. Ref.7
Tissue specificity	In all human cell types so far analyzed.
Involvement in disease	Alterations of AKT2 may contribute to the pathogenesis of ovarian carcinomas.
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
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	insulin receptor signaling pathway Inferred from mutant phenotype. Source: UniProtKB negative regulation of plasma membrane long-chain fatty acid transport Inferred from mutant phenotype. Source: UniProtKB positive regulation of fatty acid beta-oxidation Inferred from mutant phenotype. Source: UniProtKB positive regulation of glucose import Inferred from mutant phenotype. Source: UniProtKB positive regulation of glucose metabolic process Inferred from mutant phenotype. Source: UniProtKB positive regulation of glycogen biosynthetic process Inferred from mutant phenotype. Source: UniProtKB protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: UniProtKB protein serine/threonine kinase activity Ref.2 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC37	Q16543	1	EBI-296058,EBI-295634
GSK3B	P49841	1	EBI-296058,EBI-373586
SETDB1	Q15047	1	EBI-296058,EBI-79691
SH3RF1	Q7Z6J0	1	EBI-296058,EBI-311339

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 481

481

RAC-beta serine/threonine-protein kinase

PRO_0000085608

Regions

Domain

5 – 108

104

PH

Domain

152 – 409

258

Protein kinase

Domain

410 – 481

72

AGC-kinase C-terminal

Nucleotide binding

158 – 166

9

ATP By similarity

Sites

Active site

275

1

Proton acceptor By similarity

Binding site

181

1

ATP By similarity

Amino acid modifications

Modified residue

126

1

Phosphoserine Ref.9

Modified residue

309

1

Phosphothreonine; by PDPK1 Ref.6 Ref.8

Modified residue

474

1

Phosphoserine Ref.8

Natural variations

Natural variant

188

1

I → V Ref.11

VAR_040356

Natural variant

208

1

R → K: dbSNP rs35817154. Ref.11

VAR_040357

Experimental info

Mutagenesis

309

1

T → E: Constitutively active; when associated with D-474. Ref.8

Mutagenesis

474

1

S → D: Constitutively active; when associated with E-309. Ref.8

Sequence conflict

478 – 481

4

SIRE → FREEKDLLMSLFVSLILFSD FSSLKSHSFSSNFILLSFSS LKK in AAA36585. Ref.1

Secondary structure

1

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481

Helix Strand Turn

Details...

Beta strand

6 – 15

10

Beta strand

17 – 20

4

Beta strand

22 – 30

9

Turn

31 – 33

3

Beta strand

34 – 40

7

Beta strand

45 – 47

3

Beta strand

52 – 56

5

Beta strand

58 – 60

3

Beta strand

62 – 65

4

Beta strand

67 – 75

9

Beta strand

86 – 92

7

Helix

93 – 110

18

Helix

149 – 151

3

Beta strand

152 – 160

9

Beta strand

162 – 171

10

Turn

172 – 174

3

Beta strand

177 – 184

8

Turn

185 – 187

3

Turn

199 – 202

4

Helix

203 – 206

4

Beta strand

215 – 220

6

Beta strand

222 – 230

9

Helix

237 – 242

6

Helix

249 – 268

20

Helix

278 – 280

3

Beta strand

281 – 283

3

Beta strand

289 – 291

3

Helix

319 – 324

6

Helix

330 – 345

16

Beta strand

351 – 353

3

Helix

358 – 364

7

Helix

375 – 384

10

Helix

389 – 391

3

Turn

397 – 399

3

Helix

400 – 404

5

Helix

414 – 418

5

Sequences

	Sequence		Length	Mass (Da)
	P31751-1 [UniParc]. Last modified November 1, 1995. Version 2. Checksum: B18C87A7246BFB24	FASTA	481	55,769
	10 20 30 40 50 60 MNEVSVIKEG WLHKRGEYIK TWRPRYFLLK SDGSFIGYKE RPEAPDQTLP PLNNFSVAEC 70 80 90 100 110 120 QLMKTERPRP NTFVIRCLQW TTVIERTFHV DSPDEREEWM RAIQMVANSL KQRAPGEDPM 130 140 150 160 170 180 DYKCGSPSDS STTEEMEVAV SKARAKVTMN DFDYLKLLGK GTFGKVILVR EKATGRYYAM 190 200 210 220 230 240 KILRKEVIIA KDEVAHTVTE SRVLQNTRHP FLTALKYAFQ THDRLCFVME YANGGELFFH 250 260 270 280 290 300 LSRERVFTEE RARFYGAEIV SALEYLHSRD VVYRDIKLEN LMLDKDGHIK ITDFGLCKEG 310 320 330 340 350 360 ISDGATMKTF CGTPEYLAPE VLEDNDYGRA VDWWGLGVVM YEMMCGRLPF YNQDHERLFE 370 380 390 400 410 420 LILMEEIRFP RTLSPEAKSL LAGLLKKDPK QRLGGGPSDA KEVMEHRFFL SINWQDVVQK 430 440 450 460 470 480 KLLPPFKPQV TSEVDTRYFD DEFTAQSITI TPPDRYDSLG LLELDQRTHF PQFSYSASIR E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a second form of rac protein kinase." Jones P.F., Jakubowicz T., Hemmings B.A. Cell Regul. 2:1001-1009(1991) [PubMed: 1801921] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Epithelium.
[2]	"AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas." Cheng J.Q., Godwin A.K., Bellacosa A., Taguchi T., Franke T.F., Hamilton T.C., Tsichlis P.N., Testa J.R. Proc. Natl. Acad. Sci. U.S.A. 89:9267-9271(1992) [PubMed: 1409633] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[4]	"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].
[5]	NIEHS SNPs program Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 237-277.
[6]	"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-309 BY PDPK1.
[7]	"The protooncogene TCL1 is an Akt kinase coactivator." Laine J., Kuenstle G., Obata T., Sha M., Noguchi M. Mol. Cell 6:395-407(2000) [PubMed: 10983986] [Abstract] Cited for: INTERACTION WITH MTCP1; TCL1A AND TCL1B.
[8]	"Activation of a GST-tagged AKT2/PKBbeta." Baer K., Lisinski I., Gompert M., Stuhlmann D., Schmolz K., Klein H.W., Al-Hasani H. Biochim. Biophys. Acta 1725:340-347(2005) [PubMed: 15890450] [Abstract] Cited for: MUTAGENESIS OF THR-309 AND SER-474, PHOSPHORYLATION AT THR-309 AND SER-474.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126, MASS SPECTROMETRY.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"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: VARIANTS [LARGE SCALE ANALYSIS] VAL-188 AND LYS-208.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

M77198 mRNA. Translation: AAA36585.1.
M95936 mRNA. Translation: AAA58364.1.
AK314619 mRNA. Translation: BAG37185.1.
BC120994 mRNA. Translation: AAI20995.1.
AY708392 Genomic DNA. Translation: AAT97984.1.

IPI

IPI00012870.

PIR

A46288.

RefSeq

NP_001617.1.

UniGene

Hs.631535

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GZK	X-ray	2.30	A	146-460	[»]
1GZN	X-ray	2.50	A	146-480	[»]
1GZO	X-ray	2.75	A	146-460	[»]
1MRV	X-ray	2.80	A	143-481	[»]
1MRY	X-ray	2.80	A	143-481	[»]
1O6K	X-ray	1.70	A	146-481	[»]
1O6L	X-ray	1.60	A	146-467	[»]
1P6S	NMR	-	A	1-111	[»]
2JDO	X-ray	1.80	A	146-467	[»]
2JDR	X-ray	2.30	A	146-467	[»]
2UW9	X-ray	2.10	A	146-467	[»]
3D0E	X-ray	2.00	A/B	146-480	[»]
3E87	X-ray	2.30	A/B	146-480	[»]
3E88	X-ray	2.50	A/B	146-480	[»]
3E8D	X-ray	2.70	A/B	146-480	[»]

DisProt

DP00304.

ModBase

Search...

Protein-protein interaction databases

IntAct

P31751. 4 interactions.

PTM databases

PhosphoSite

P31751.

Proteomic databases

PRIDE

P31751.

Genome annotation databases

Ensembl

ENSG00000105221. Homo sapiens. [Contig view]

GeneID

208.

KEGG

hsa:208.

Organism-specific databases

GeneCards

GC19M045430.

H-InvDB

HIX0015131.

HGNC

HGNC:392. AKT2.

HPA

CAB004204.

MIM

164731. gene.

PharmGKB

PA24685.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P31751.

HOVERGEN

P31751.

OMA

P31751. XALKYAF.

Enzyme and pathway databases

BRENDA

2.7.11.1. 247.

Pathway_Interaction_DB

pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.
insulin_pathway. Insulin Pathway.
insulin_glucose_pathway. Insulin-mediated glucose transport.

Reactome

REACT_11061. Signalling by NGF.
REACT_1123. Inhibition of HSL.
REACT_13698. Regulation of beta-cell development.
REACT_498. Signaling by Insulin receptor.

Gene expression databases

ArrayExpress

P31751.

Bgee

P31751.

CleanEx

HS_AKT2.

GermOnline

ENSG00000105221. Homo sapiens.

Family and domain databases

InterPro

IPR000961. AGC-kinase_C.
IPR011993. PH_type.
IPR017892. Pkinase_C.
IPR001849. Pleckstrin_homology.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
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]

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

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

P31751.

NextBio

836.

SOURCE

Search...

Entry information

Entry name

AKT2_HUMAN

Accession

Primary (citable) accession number: P31751
Secondary accession number(s): B2RBD8, Q0VAN1, Q68GC0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	November 1, 1995
Last modified:	June 16, 2009
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)