Reviewed,
UniProtKB/Swiss-Prot Q9Y243 (AKT3_HUMAN)
Last modified
February 9, 2010.
Version 107.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
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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 |
| ||||
| 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.1Traceable author statement. Source: ProtInc |
| Cellular component | cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to membraneInferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.14Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activityInferred from electronic annotation. Source: UniProtKB-KW |
| 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.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
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References
| « Hide '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. 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. 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. 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. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-171. |
| + | Additional computationally mapped references. |
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 AL662889 Genomic DNA. Translation: CAH71866.1. AL591721 AL662889 Genomic DNA. Translation: CAH71867.1. AL592151 AL662889 Genomic DNA. Translation: CAH72891.1. AL592151 AL662889 Genomic DNA. Translation: CAH72892.1. AL662889 AL592151 Genomic DNA. Translation: CAH73072.1. AL662889 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 Q9UFP5 | ||||||||
| Entry 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. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


