Phospho-AKT2 (Ser474) Antibody
(Synonyms: PKBB; PRKBB; PKBBETA; RAC-BETA)Based on 1 Customer Validation
Phospho-AKT2 (Ser474) Antibody is a Rabbit-derived and non-conjugated IgG Polyclonal antibody, targeting to Phospho-AKT2 (Ser474).
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Host:
Rabbit
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Isotype:
IgG
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Application:
WB, IHC-P
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Reactivity :
Human, Mouse
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Formulation:
Supplied in TBS (pH7.4), 0.2% BSA, 50% Glycerol, 0.05% Sodium Azide.
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Conjugation:
Non-conjugated
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
Applications
| Application |
WB
WB: Western Blot
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IHC-P
IHC-P: Immunohistochemistry-Paraffin
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|---|---|---|
| Dilution Ratio | 1:500-2000 | 1:100-500 |
Product Details
Phospho-AKT2 (Ser474) Antibody is a Rabbit-derived and non-conjugated IgG Polyclonal antibody, targeting to Phospho-AKT2 (Ser474).
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Host Rabbit
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Species ReactivityHuman, Mouse
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Observed Molecular WeightObserved band size: 56 kDa
Note: Due to possible protein modifications or aggregation, the molecular weight should be confirmed by actual measurement, and the predicted value is for reference only.
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Calculated Molecular Weight Predicted band size: 56 kDa
Synthetic peptide within human AKT2 aa 450-481(phospho S474).
Endogenous
affinity purified
Non-conjugated
Phosphorylated
IgG
Product Properties
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Appearance
Solution
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Formulation
Supplied in TBS (pH7.4), 0.2% BSA, 50% Glycerol, 0.05% Sodium Azide.
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Concentration
Batch-dependent, Please check the COA for the concentration of each lot. Check Lot Concentration
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Storage & Stability
Stored at -20°C for 1 year. Avoid repeated freeze / thaw cycles.
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Shipping
Shipping with blue ice.
Background
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Function
AKT2 (protein kinase Bβ) is a serine/threonine kinase that functions downstream of phosphoinositide 3-kinase (PI3K) and mediates insulin-dependent regulation of glucose transport, glycogen synthesis, and metabolic homeostasis[1][2]. Mechanistically, AKT2 is a central effector of insulin receptor signaling and controls glucose utilization through phosphorylation networks linked to cellular metabolism and nutrient storage[2][3]. In disease contexts, AKT2 was originally identified as an oncogenic kinase amplified in ovarian carcinoma and later shown to contribute to malignant phenotypes in multiple tumor models through enhanced survival and growth signaling[1]. Genetic studies further established its metabolic importance, as Akt2-deficient mice develop insulin resistance, glucose intolerance, dyslipidemia, adipose tissue loss, and progressive diabetic phenotypes, supporting its essential role in systemic glucose regulation[2][3]. Compared with related isoforms, AKT1 is more strongly associated with organismal growth and developmental regulation, whereas AKT2 displays a more specialized function in insulin-responsive tissues and metabolic control[4][5]. Isoform-specific analyses in skeletal muscle from patients with type 2 diabetes demonstrated impaired insulin-stimulated AKT2 activation and altered phosphorylation patterns, linking defective AKT2 signaling to human metabolic disease[6]. For experimental applications, ATP-competitive AKT inhibitors such as GSK690693 directly target the AKT kinase domain and are widely used to investigate AKT-dependent signaling mechanisms in cancer and metabolic research models[7].
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Subcellular Localization
Cytoplasm; Nucleus; Cell membrane; Mitochondrion intermembrane space
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Expression
Tissue_specificity:This protein is expressed in prostate cancer, and its expression level gradually increases from normal to malignant (protein level) . It is expressed in all human cell types analyzed to date. The phosphorylated form of Tyr-176 is significantly increased in the progressive stages of breast cancer (i.e., from normal to hyperplastic (ADH) , ductal carcinoma in situ (DCIS) , invasive ductal carcinoma (IDC) , and lymph node metastasis (LNMM) stages) . -
Isoforms & Post-Translational Modification
P31749 has 2 isomers: P31749-1: 55686 Da (predicted); P31749-2: 48347 Da (predicted).
O-GlcNAcylation at Thr-305 and Thr-312 inhibits activating phosphorylation at Thr-308 via disrupting the interaction between AKT1 and PDPK1. O-GlcNAcylation at Ser-473 also probably interferes with phosphorylation at this site;Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for full activity (PubMed:12149249, PubMed:15047712, PubMed:15262962, PubMed:16266983, PubMed:18456494, PubMed:20481595, PubMed:20978158, PubMed:8978681, PubMed:9512493, PubMed:9736715). Phosphorylation of the activation loop at Thr-308 by PDPK1/PDK1 is a prerequisite for full activation (PubMed:9512493). Phosphorylation by mTORC2 in response to growth factors plays a key role in AKT1 activation: mTORC2 phosphorylates different sites depending on the context, such as Thr-450, Ser-473, Ser-477 or Thr-479, thereby facilitating subsequent phosphorylation of the activation loop by PDPK1/PDK1 (PubMed:15718470, PubMed:24670654). Phosphorylation at Ser-473 by mTORC2 promotes ubiquitination and degradation by the proteasome (By similarity). Also phosphorylated at Ser-477 and Thr-479 by CDK2, facilitating subsequent phosphorylation of the activation loop by PDPK1/PDK1 (PubMed:24670654). Activated TNK2 phosphorylates it on Tyr-176 resulting in its binding to the anionic plasma membrane phospholipid PA (PubMed:20333297). This phosphorylated form localizes to the cell membrane, where it is targeted by PDPK1 and PDPK2 for further phosphorylations on Thr-308 and Ser-473 leading to its activation (PubMed:20333297). Phosphorylated at Thr-308 and Ser-473 by IKBKE and TBK1 (PubMed:21464307). Ser-473 phosphorylation is enhanced by interaction with AGAP2 isoform 2 (PIKE-A) (PubMed:14761976). Ser-473 phosphorylation is enhanced in focal cortical dysplasias with Taylor-type balloon cells (PubMed:17013611). Ser-473 phosphorylation is enhanced by signaling through activated FLT3 (PubMed:16266983). Ser-473 is dephosphorylated by PHLPP (PubMed:28147277). Dephosphorylated at Thr-308 and Ser-473 by PP2A phosphatase (PubMed:21329884). The phosphorylated form of PPP2R5B is required for bridging AKT1 with PP2A phosphatase (PubMed:21329884). Ser-473 is dephosphorylated by CPPED1, leading to termination of signaling (PubMed:23799035). AIM2 acts as an inhibitor of AKT1 by inhibiting phosphorylation Ser-473: AIM2 acts both by inhibiting the activity of PRKDC/DNA-PK kinase and promoting dephosphorylation by PP2A phosphatase (By similarity);Ubiquitinated; undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. TRAF6-induced 'Lys-63'-linked AKT1 ubiquitination is critical for phosphorylation and activation (PubMed:19713527). When ubiquitinated, it translocates to the plasma membrane, where it becomes phosphorylated (PubMed:20059950). When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome (PubMed:20059950). Also ubiquitinated by TRIM13 leading to its proteasomal degradation (PubMed:21333377). Phosphorylated, undergoes 'Lys-48'-linked polyubiquitination preferentially at Lys-284 catalyzed by MUL1, leading to its proteasomal degradation (PubMed:22410793). Ubiquitinated via 'Lys-48'-linked polyubiquitination by ZNRF1, leading to its degradation by the proteasome (By similarity);Acetylated on Lys-14 and Lys-20 by the histone acetyltransferases EP300 and KAT2B. Acetylation results in reduced phosphorylation and inhibition of activity. Deacetylated at Lys-14 and Lys-20 by SIRT1. SIRT1-mediated deacetylation relieves the inhibition;Cleavage by caspase-3/CASP3 (By similarity). Cleaved at the caspase-3 consensus site Asp-462 during apoptosis, resulting in down-regulation of the AKT signaling pathway and decreased cell survival (PubMed:23152800) -
Subunit
Interacts with BTBD10 (By similarity). Interacts with KCTD20 (By similarity). Interacts (via the C-terminus) with CCDC88A (via its C-terminus). Interacts with GRB10; the interaction leads to GRB10 phosphorylation thus promoting YWHAE-binding (By similarity). Interacts with AGAP2 (isoform 2/PIKE-A); the interaction occurs in the presence of guanine nucleotides. Interacts with AKTIP. Interacts (via PH domain) with MTCP1, TCL1A and TCL1B. Interacts with CDKN1B; the interaction phosphorylates CDKN1B promoting 14-3-3 binding and cell-cycle progression. Interacts with MAP3K5 and TRAF6. Interacts with BAD, PPP2R5B, STK3 and STK4. Interacts (via PH domain) with SIRT1. Interacts with SRPK2 in a phosphorylation-dependent manner. Interacts with RAF1. Interacts with TRIM13; the interaction ubiquitinates AKT1 leading to its proteasomal degradation. Interacts with TNK2 and CLK2. Interacts (via the C-terminus) with THEM4 (via its C-terminus). Interacts with and phosphorylated by PDPK1. Interacts with PA2G4 (By similarity). Interacts with KIF14; the interaction is detected in the plasma membrane upon INS stimulation and promotes AKT1 phosphorylation (PubMed:24784001). Interacts with FAM83B; activates the PI3K/AKT signaling cascade (PubMed:23676467). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529). Forms a complex with WDFY2 and FOXO1 (By similarity). Interacts with FAM168A (PubMed:23251525). Interacts with SYAP1 (via phosphorylated form and BSD domain); this interaction is enhanced in a mTORC2-mediated manner in response to epidermal growth factor (EGF) stimulation and activates AKT1 (PubMed:23300339). Interacts with PKHM3 (By similarity). Interacts with FKBP5/FKBP51; promoting interaction between Akt/AKT1 and PHLPP1, thereby enhancing dephosphorylation and subsequent activation of Akt/AKT1 (PubMed:28147277). Interacts with TMEM175; leading to formation of the lysoK(GF) complex (PubMed:32228865). Acts as a negative regulator of the cGAS-STING pathway by mediating phosphorylation of CGAS during mitosis, leading to its inhibition (PubMed:26440888)
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SwissProt ID
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Synonyms
PKBB; PRKBB; PKBBETA; RAC-BETA
Documentation
References
[1]. Cheng JQ, et al. AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9267-71. [Content Brief]
[2]. Cho H, et al. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science. 2001 Jun 1;292(5522):1728-31. [Content Brief]
[3]. Garofalo RS, et al. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta. J Clin Invest. 2003 Jul;112(2):197-208. [Content Brief]
[4]. Alibardi L. Stimulation of regenerative blastema formation in lizards as a model to analyze limb regeneration in amniotes. Histol Histopathol. 2019 Oct;34(10):1111-1120. doi: 10.14670/HH-18-123. Epub 2019 May 6. PMID: 31058307. et al. Stimulation of regenerative blastema formation in lizards as a model to analyze limb regeneration in amniotes. Histol Histopathol. 2019 Oct;34(10):1111-1120. [Content Brief]
[5]. Irie HY, et al. Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition. J Cell Biol. 2005 Dec 19;171(6):1023-34. [Content Brief]
[6]. Cozzone D, et al. Isoform-specific defects of insulin stimulation of Akt/protein kinase B (PKB) in skeletal muscle cells from type 2 diabetic patients. Diabetologia. 2008 Mar;51(3):512-21. [Content Brief]
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