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Entry version 253 (23 Feb 2022)
Sequence version 2 (01 Feb 2005)
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Protein

RAC-alpha serine/threonine-protein kinase

Gene

AKT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

AKT1 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 (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781).

This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781).

Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781).

AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface (By similarity).

Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity).

Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (PubMed:11994271).

AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity (By similarity).

Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity).

AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase) (PubMed:11154276).

Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis (PubMed:11154276).

AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1 (PubMed:12150915).

AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization (PubMed:10358075).

In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PubMed:10358075).

FOXO3 and FOXO4 are phosphorylated on equivalent sites (PubMed:10358075).

AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein) (PubMed:9829964).

The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1 (PubMed:9829964).

AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity).

Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity).

Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI3P-5 activity (By similarity).

The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity).

Signals downstream of phosphatidylinositol 3-kinase (PI3K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I) (PubMed:12176338, PubMed:12964941).

AKT mediates the antiapoptotic effects of IGF-I (By similarity).

Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221).

May be involved in the regulation of the placental development (By similarity).

Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3 (PubMed:17726016).

Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation (PubMed:20086174, PubMed:20231902).

Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (PubMed:19592491).

Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (PubMed:10576742).

Phosphorylation of BAD stimulates its pro-apoptotic activity (PubMed:10926925).

Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (PubMed:23431171).

Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility (PubMed:20471940).

Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation (PubMed:18507042).

Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization (PubMed:16982699).

These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation (PubMed:16139227).

Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (PubMed:20682768).

Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor (PubMed:32322062).

Also acts as an activator of TMEM175 potassium channel activity in response to growth factors: forms the lysoK(GF) complex together with TMEM175 and acts by promoting TMEM175 channel activation, independently of its protein kinase activity (PubMed:32228865).

4 PublicationsBy similarity22 Publications

Miscellaneous

(2S)-2-(4-chlorobenzyl)-3-oxo-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]propan-1-amine corresponds to compound 44.1 Publication
5-(5-chloro-1H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine corresponds to compound 8b.1 Publication

Caution

PUBMED:19940129 has been retracted because the same data were used to represent different experimental conditions.2 Publications
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.Curated

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Three specific sites, one in the kinase domain (Thr-308) and the two other ones in the C-terminal regulatory region (Ser-473 and Tyr-474), need to be phosphorylated for its full activation. Inhibited by pyrrolopyrimidine inhibitors like aniline triazole and spiroindoline.6 Publications

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=52.8 µM for ATP (for purified and in vitro activated AKT1)1 Publication
  2. KM=0.5 µM for peptide substrate (for purified and in vitro activated AKT1)1 Publication
  3. KM=143.3 µM for ATP (for recombinant myristoylated AKT1 expressed and immunoprecipitated from Rat-1 cells)1 Publication
  4. KM=2.9 µM for peptide substrate (for recombinant myristoylated AKT1 expressed and immunoprecipitated from Rat-1 cells)1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei53Inositol-(1,3,4,5)-tetrakisphosphate2 Publications1
Binding sitei86Inositol-(1,3,4,5)-tetrakisphosphate2 Publications1
Binding sitei179ATPPROSITE-ProRule annotation1
Binding sitei2345-(5-chloro-1H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine; inhibitorCombined sources1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei274Proton acceptorPROSITE-ProRule annotation1
Binding sitei278(2S)-2-(4-chlorobenzyl)-3-oxo-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]propan-1-amine; inhibitor; via carbonyl oxygenCombined sources1 Publication1
Binding sitei292(2S)-2-(4-chlorobenzyl)-3-oxo-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]propan-1-amine; inhibitorCombined sources1 Publication1
Binding sitei2925-(5-chloro-1H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine; inhibitorCombined sources1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi156 – 164ATPPROSITE-ProRule annotation9

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionDevelopmental protein, Kinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Carbohydrate metabolism, Glucose metabolism, Glycogen biosynthesis, Glycogen metabolism, Neurogenesis, Sugar transport, Translation regulation, Transport
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.7.11.1, 2681

Pathway Commons web resource for biological pathway data

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PathwayCommonsi
P31749

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-111447, Activation of BAD and translocation to mitochondria
R-HSA-1257604, PIP3 activates AKT signaling
R-HSA-1358803, Downregulation of ERBB2:ERBB3 signaling
R-HSA-1445148, Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-1474151, Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
R-HSA-165159, MTOR signalling
R-HSA-198323, AKT phosphorylates targets in the cytosol
R-HSA-198693, AKT phosphorylates targets in the nucleus
R-HSA-199418, Negative regulation of the PI3K/AKT network
R-HSA-203615, eNOS activation
R-HSA-211163, AKT-mediated inactivation of FOXO1A
R-HSA-354192, Integrin signaling
R-HSA-3769402, Deactivation of the beta-catenin transactivating complex
R-HSA-389357, CD28 dependent PI3K/Akt signaling
R-HSA-389513, CTLA4 inhibitory signaling
R-HSA-392451, G beta:gamma signalling through PI3Kgamma
R-HSA-450385, Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
R-HSA-450604, KSRP (KHSRP) binds and destabilizes mRNA
R-HSA-5218920, VEGFR2 mediated vascular permeability
R-HSA-5628897, TP53 Regulates Metabolic Genes
R-HSA-5674400, Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-6785807, Interleukin-4 and Interleukin-13 signaling
R-HSA-6804757, Regulation of TP53 Degradation
R-HSA-6804758, Regulation of TP53 Activity through Acetylation
R-HSA-6804759, Regulation of TP53 Activity through Association with Co-factors
R-HSA-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-69202, Cyclin E associated events during G1/S transition
R-HSA-69656, Cyclin A:Cdk2-associated events at S phase entry
R-HSA-8849469, PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1
R-HSA-8876198, RAB GEFs exchange GTP for GDP on RABs
R-HSA-8941332, RUNX2 regulates genes involved in cell migration
R-HSA-8948751, Regulation of PTEN stability and activity
R-HSA-9009391, Extra-nuclear estrogen signaling
R-HSA-9604323, Negative regulation of NOTCH4 signaling
R-HSA-9607240, FLT3 Signaling
R-HSA-9614399, Regulation of localization of FOXO transcription factors
R-HSA-9634638, Estrogen-dependent nuclear events downstream of ESR-membrane signaling

SABIO-RK: Biochemical Reaction Kinetics Database

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SABIO-RKi
P31749

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
P31749

SIGNOR Signaling Network Open Resource

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SIGNORi
P31749

Protein family/group databases

Transport Classification Database

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TCDBi
8.A.104.1.10, the 5'-amp-activated protein kinase (ampk) family

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
RAC-alpha serine/threonine-protein kinase (EC:2.7.11.11 Publication)
Alternative name(s):
Protein kinase B
Short name:
PKB
Protein kinase B alpha
Short name:
PKB alpha
Proto-oncogene c-Akt
RAC-PK-alpha
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:AKT1
Synonyms:PKB, RAC
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 14

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:391, AKT1

Online Mendelian Inheritance in Man (OMIM)

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MIMi
164730, gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_P31749

Eukaryotic Pathogen, Vector and Host Database Resources

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VEuPathDBi
HostDB:ENSG00000142208

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Breast cancer (BC)1 Publication
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease descriptionA common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
Related information in OMIM
Colorectal cancer (CRC)
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Related information in OMIM
Genetic variations in AKT1 may play a role in susceptibility to ovarian cancer.
Proteus syndrome (PROTEUSS)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA highly variable, severe disorder of asymmetric and disproportionate overgrowth of body parts, connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. Many features of Proteus syndrome overlap with other overgrowth syndromes.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_05542217E → K in PROTEUSS and breast cancer; also detected in colorectal and ovarian cancer; somatic mutation; results in increased phosphorylation at T-308 and higher basal ubiquitination; the mutant protein is more efficiently recruited to the plasma membrane; alters phosphatidylinositiol phosphates lipid specificity of the AKT1 PH domain. 4 PublicationsCorresponds to variant dbSNP:rs121434592EnsemblClinVar.1
Cowden syndrome 6 (CWS6)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of Cowden syndrome, a hamartomatous polyposis syndrome with age-related penetrance. Cowden syndrome is characterized by hamartomatous lesions affecting derivatives of ectodermal, mesodermal and endodermal layers, macrocephaly, facial trichilemmomas (benign tumors of the hair follicle infundibulum), acral keratoses, papillomatous papules, and elevated risk for development of several types of malignancy, particularly breast carcinoma in women and thyroid carcinoma in both men and women. Colon cancer and renal cell carcinoma have also been reported. Hamartomas can be found in virtually every organ, but most commonly in the skin, gastrointestinal tract, breast and thyroid.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06979125R → C in CWS6. 1 PublicationCorresponds to variant dbSNP:rs397514644EnsemblClinVar.1
Natural variantiVAR_069792435T → P in CWS6. 1 PublicationCorresponds to variant dbSNP:rs397514645EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi8K → R: Substantial reduction of ubiquitination, phosphorylation at T-308 and S-473, AKT activation as well as IGF1-induced membrane recruitment. Decrease in ubiquitination and phosphorylation at T-308 as well as impaired association with the membrane; when associated with K-17. 1 Publication1
Mutagenesisi14K → A: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. 3 Publications1
Mutagenesisi14K → Q: Substantial reduction of phosphorylation at T-308 and S-473, loss of AKT activation, and loss of binding to PIP3 as well as IGF1-induced membrane recruitment. 3 Publications1
Mutagenesisi14K → R: Substantial reduction of ubiquitination, phosphorylation at T-308 and S-473, AKT activation, loss of binding to PIP3 as well as IGF1-induced membrane recruitment. 3 Publications1
Mutagenesisi17E → K: No effect on membrane localization. Loss of membrane localization; when associated with Q-20. 1 Publication1
Mutagenesisi20K → Q: Substantial reduction of phosphorylation at T-308 and S-473, reduced AKT activation, and reduced binding to PIP3 as well as IGF1-induced membrane recruitment. Loss of membrane localization; when associated with K-17. 1 Publication1
Mutagenesisi20K → R: Slight increase of phosphorylation at T-308 and S-473. 1 Publication1
Mutagenesisi25R → A or C: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. 1 Publication1
Mutagenesisi86R → A: Impairs interaction with PtdIns(3,4,5)P3 and PtdIns(3,4)P2. 1 Publication1
Mutagenesisi176Y → F: Significant loss of interaction with TNK2. Loss of membrane localization. Significant reduction in phosphorylation on Ser-473. 1 Publication1
Mutagenesisi305T → A: Reduces O-GlcNAc levels; Reduces O-GlcNAc levels even more; when associated with A-312. 1 Publication1
Mutagenesisi305T → Y: Abolishes phosphorylation at Thr-308. 1 Publication1
Mutagenesisi308T → D: 5-fold activation and 18-fold activation; when associated with D-473. 2 Publications1
Mutagenesisi312T → A: Reduces O-GlcNAc levels; Reduces O-GlcNAc levels even more; when associated with A-305. 1 Publication1
Mutagenesisi312T → Y: Abolishes phosphorylation at Thr-308. 1 Publication1
Mutagenesisi473S → D: 7-fold activation and 25-fold activation; when associated with D-308. 2 Publications1
Mutagenesisi474Y → F: 55% inhibition of activation. 1 Publication1

Keywords - Diseasei

Disease variant, Proto-oncogene

Organism-specific databases

DisGeNET

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DisGeNETi
207

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

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GeneReviewsi
AKT1

MalaCards human disease database

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MalaCardsi
AKT1
MIMi114480, phenotype
114500, phenotype
176920, phenotype
615109, phenotype

Open Targets

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OpenTargetsi
ENSG00000142208

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
201, Cowden syndrome
2495, Meningioma
744, Proteus syndrome

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA24684

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
P31749, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL4282

Drug and drug target database

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DrugBanki
DB07585, 5-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine
DB05971, Archexin
DB01169, Arsenic trioxide
DB00171, ATP
DB06486, Enzastaurin
DB01645, Genistein
DB01863, Inositol 1,3,4,5-Tetrakisphosphate
DB07584, N-[2-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine
DB06641, Perifosine
DB02709, Resveratrol

DrugCentral

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DrugCentrali
P31749

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
1479

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
AKT1

Domain mapping of disease mutations (DMDM)

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DMDMi
60391226

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000856051 – 480RAC-alpha serine/threonine-protein kinaseAdd BLAST480

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei14N6-acetyllysine1 Publication1
Modified residuei20N6-acetyllysine1 Publication1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi60 ↔ 771 Publication
Modified residuei124PhosphoserineCombined sources1
Modified residuei126Phosphoserine; alternateCombined sources1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi126O-linked (GlcNAc) serine; alternate1 Publication1
Modified residuei129Phosphoserine; alternateCombined sources1
Glycosylationi129O-linked (GlcNAc) serine; alternate1 Publication1
Modified residuei176Phosphotyrosine; by TNK21 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki284Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Disulfide bondi296 ↔ 310By similarity
Glycosylationi305O-linked (GlcNAc) threonine1 Publication1
Modified residuei308Phosphothreonine; by IKKE, PDPK1 and TBK17 Publications1
Glycosylationi312O-linked (GlcNAc) threonine1 Publication1
Modified residuei448PhosphothreonineCombined sources1
Modified residuei450PhosphothreonineCombined sources1
Modified residuei473Phosphoserine; by IKKE, MTOR and TBK1; alternate11 Publications1
Glycosylationi473O-linked (GlcNAc) serine; alternateBy similarity1
Modified residuei474Phosphotyrosine1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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.14 Publications
Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required for full activity (PubMed:12149249, PubMed:14761976, PubMed:15047712, PubMed:16266983, PubMed:17013611, PubMed:20978158, PubMed:9736715, PubMed:23799035, PubMed:8978681, PubMed:28147277). 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:9512493). Ser-473 phosphorylation by mTORC2 favors Thr-308 phosphorylation by PDPK1 (PubMed:21464307, PubMed:8978681). Phosphorylated at Thr-308 and Ser-473 by IKBKE and TBK1 (PubMed:15718470, PubMed:18456494, PubMed:20481595, PubMed:8978681). 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 (By similarity). 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:9512493).By similarity17 Publications
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).By similarity4 Publications
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.1 Publication
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).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei462Cleavage; by caspase-3By similarity1

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

The CPTAC Assay portal

More...
CPTACi
CPTAC-783
CPTAC-784

Encyclopedia of Proteome Dynamics

More...
EPDi
P31749

jPOST - Japan Proteome Standard Repository/Database

More...
jPOSTi
P31749

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...
MassIVEi
P31749

MaxQB - The MaxQuant DataBase

More...
MaxQBi
P31749

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
P31749

PeptideAtlas

More...
PeptideAtlasi
P31749

PRoteomics IDEntifications database

More...
PRIDEi
P31749

ProteomicsDB: a multi-organism proteome resource

More...
ProteomicsDBi
54800 [P31749-1]
6712

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...
GlyGeni
P31749, 6 sites, 1 O-linked glycan (6 sites)

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P31749

MetOSite database of methionine sulfoxide sites

More...
MetOSitei
P31749

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
P31749

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Expressed in all human cell types so far analyzed. The Tyr-176 phosphorylated form shows a significant increase in expression in breast cancers during the progressive stages i.e. normal to hyperplasia (ADH), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and lymph node metastatic (LNMM) stages.3 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000142208, Expressed in left adrenal gland and 233 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
P31749, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
P31749, HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
ENSG00000142208, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

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).

By similarity36 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

P31749
With#Exp.IntAct
ADAMTSL4 - isoform 3 [Q6UY14-3]3EBI-296087,EBI-10173507
itself3EBI-296087,EBI-296087
ALYREF [Q86V81]5EBI-296087,EBI-347640
ASXL1 [Q8IXJ9]2EBI-296087,EBI-1646500
ATXN1 [P54253]6EBI-296087,EBI-930964
BCL10 [O95999]5EBI-296087,EBI-958922
BTBD1 [Q9H0C5]3EBI-296087,EBI-935503
CAMK2A [Q9UQM7]3EBI-296087,EBI-1383687
CCNA2 [P20248]2EBI-296087,EBI-457097
CDC37 [Q16543]4EBI-296087,EBI-295634
CEP76 [Q8TAP6]3EBI-296087,EBI-742887
CREBBP [Q92793]3EBI-296087,EBI-81215
CYTH1 [Q15438]3EBI-296087,EBI-997830
DDIT4L [Q96D03]3EBI-296087,EBI-742054
DNMT1 [P26358]6EBI-296087,EBI-719459
FAM110C [Q1W6H9]2EBI-296087,EBI-3942563
FOXO1 [Q12778]2EBI-296087,EBI-1108782
FOXO3 [O43524]3EBI-296087,EBI-1644164
FYN [P06241]3EBI-296087,EBI-515315
GAL [P22466]3EBI-296087,EBI-6624768
GSK3B [P49841]4EBI-296087,EBI-373586
HSFY2 - isoform 3 [Q96LI6-3]3EBI-296087,EBI-25830912
HSP90AB1 [P08238]3EBI-296087,EBI-352572
HTT [P42858]3EBI-296087,EBI-466029
LRRK2 [Q5S007]6EBI-296087,EBI-5323863
MAP3K5 [Q99683]2EBI-296087,EBI-476263
MAPT [P10636]2EBI-296087,EBI-366182
MDM2 [Q00987]4EBI-296087,EBI-389668
MESD [Q14696]3EBI-296087,EBI-6165891
MTOR [P42345]4EBI-296087,EBI-359260
NIBAN1 [Q9BZQ8]2EBI-296087,EBI-6916466
NR3C1 [P04150]5EBI-296087,EBI-493507
PDPK1 [O15530]4EBI-296087,EBI-717097
PEBP4 [Q96S96]2EBI-296087,EBI-8563667
PLCG1 [P19174]9EBI-296087,EBI-79387
PPL [O60437]2EBI-296087,EBI-368321
PPP1CA [P62136]4EBI-296087,EBI-357253
PPP2CA [P67775]4EBI-296087,EBI-712311
PPP2R1A [P30153]2EBI-296087,EBI-302388
PRKACA [P17612]3EBI-296087,EBI-476586
PRKCZ [Q05513]2EBI-296087,EBI-295351
PRUNE2 [A0A0C4DFM3]3EBI-296087,EBI-25830870
SETDB1 [Q15047]9EBI-296087,EBI-79691
SIRT1 [Q96EB6]5EBI-296087,EBI-1802965
STK4 [Q13043]13EBI-296087,EBI-367376
STUB1 - isoform 1 [Q9UNE7-1]5EBI-296087,EBI-15687717
TCL1A [P56279]8EBI-296087,EBI-749995
TERF2IP [Q9NYB0]2EBI-296087,EBI-750109
THEM4 [Q5T1C6]4EBI-296087,EBI-7684443
TOPBP1 [Q92547]2EBI-296087,EBI-308302
TTC3 [P53804]4EBI-296087,EBI-2681313
TXN [P10599]3EBI-296087,EBI-594644
VIM [P08670]29EBI-296087,EBI-353844
XAF1 [Q6GPH4]3EBI-296087,EBI-2815120
ZNF24 [A0A024RC47]3EBI-296087,EBI-25830832
Arrb2 [P29067] from Rattus norvegicus.2EBI-296087,EBI-1636616
m005R [Q83730] from Myxoma virus (strain Lausanne).3EBI-296087,EBI-6859930
X [P03165] from Hepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979).3EBI-296087,EBI-7683985
Isoform 1 [P31749-1]
With#Exp.IntAct
PDK1 - isoform 1 [Q15118-1]2EBI-12562306,EBI-12562315

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...
BioGRIDi
106710, 461 interactors

CORUM comprehensive resource of mammalian protein complexes

More...
CORUMi
P31749

Database of interacting proteins

More...
DIPi
DIP-24269N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...
ELMi
P31749

Protein interaction database and analysis system

More...
IntActi
P31749, 207 interactors

Molecular INTeraction database

More...
MINTi
P31749

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000451828

Chemistry databases

BindingDB database of measured binding affinities

More...
BindingDBi
P31749

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...
RNActi
P31749, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1480
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P31749

Database of comparative protein structure models

More...
ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

More...
PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
P31749

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini5 – 108PHPROSITE-ProRule annotationAdd BLAST104
Domaini150 – 408Protein kinasePROSITE-ProRule annotationAdd BLAST259
Domaini409 – 480AGC-kinase C-terminalPROSITE-ProRule annotationAdd BLAST72

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni14 – 19Inositol-(1,3,4,5)-tetrakisphosphate binding2 Publications6
Regioni23 – 25Inositol-(1,3,4,5)-tetrakisphosphate binding2 Publications3
Regioni113 – 138DisorderedSequence analysisAdd BLAST26
Regioni228 – 230(2S)-2-(4-chlorobenzyl)-3-oxo-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]propan-1-amine binding; inhibitorCombined sources1 Publication3
Regioni228 – 2305-(5-chloro-1H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine binding; inhibitorCombined sources1 Publication3
Regioni278 – 279(2S)-2-(4-chlorobenzyl)-3-oxo-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]propan-1-amine binding; inhibitorCombined sources1 Publication2
Regioni450 – 480DisorderedSequence analysisAdd BLAST31

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

Binding of the PH domain to phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) following phosphatidylinositol 3-kinase alpha (PIK3CA) activity results in its targeting to the plasma membrane. The PH domain mediates interaction with TNK2 and Tyr-176 is also essential for this interaction.2 Publications
The AGC-kinase C-terminal mediates interaction with THEM4.1 Publication

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG0690, Eukaryota

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000158752

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
CLU_000288_11_0_1

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
P31749

Identification of Orthologs from Complete Genome Data

More...
OMAi
CIDNERR

Database for complete collections of gene phylogenies

More...
PhylomeDBi
P31749

TreeFam database of animal gene trees

More...
TreeFami
TF102004

Family and domain databases

Conserved Domains Database

More...
CDDi
cd01241, PH_PKB, 1 hit
cd05594, STKc_PKB_alpha, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
2.30.29.30, 1 hit

Intrinsically Disordered proteins with Extensive Annotations and Literature

More...
IDEALi
IID00412

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR000961, AGC-kinase_C
IPR034676, Akt1
IPR011009, Kinase-like_dom_sf
IPR011993, PH-like_dom_sf
IPR001849, PH_domain
IPR039026, PH_PKB
IPR017892, Pkinase_C
IPR000719, Prot_kinase_dom
IPR017441, Protein_kinase_ATP_BS
IPR039027, RAC_alpha
IPR008271, Ser/Thr_kinase_AS

The PANTHER Classification System

More...
PANTHERi
PTHR24351:SF200, PTHR24351:SF200, 1 hit

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00169, PH, 1 hit
PF00069, Pkinase, 1 hit
PF00433, Pkinase_C, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00233, PH, 1 hit
SM00133, S_TK_X, 1 hit
SM00220, S_TKc, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF56112, SSF56112, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in 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

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P31749-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQREA
60 70 80 90 100
PLNNFSVAQC QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWT
110 120 130 140 150
TAIQTVADGL KKQEEEEMDF RSGSPSDNSG AEEMEVSLAK PKHRVTMNEF
160 170 180 190 200
EYLKLLGKGT FGKVILVKEK ATGRYYAMKI LKKEVIVAKD EVAHTLTENR
210 220 230 240 250
VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS RERVFSEDRA
260 270 280 290 300
RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI
310 320 330 340 350
KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY
360 370 380 390 400
NQDHEKLFEL ILMEEIRFPR TLGPEAKSLL SGLLKKDPKQ RLGGGSEDAK
410 420 430 440 450
EIMQHRFFAG IVWQHVYEKK LSPPFKPQVT SETDTRYFDE EFTAQMITIT
460 470 480
PPDQDDSMEC VDSERRPHFP QFSYSASGTA
Length:480
Mass (Da):55,686
Last modified:February 1, 2005 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i6EAFF4F8AD436714
GO
Isoform 2 (identifier: P31749-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-62: Missing.

Show »
Length:418
Mass (Da):48,347
Checksum:i671C0EB4BDF8F45F
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A804HJM6A0A804HJM6_HUMAN
Non-specific serine/threonine prote...
AKT1
505Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
G3V2I6G3V2I6_HUMAN
RAC-alpha serine/threonine-protein ...
AKT1
184Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
G3V3X1G3V3X1_HUMAN
RAC-alpha serine/threonine-protein ...
AKT1
170Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A087WY56A0A087WY56_HUMAN
RAC-alpha serine/threonine-protein ...
AKT1
146Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti173 – 174GR → A in CAA43372 (PubMed:1718748).Curated2
Sequence conflicti202L → Q in CAA43372 (PubMed:1718748).Curated1
Sequence conflicti212A → R in CAA43372 (PubMed:1718748).Curated1
Sequence conflicti246S → A in CAA43372 (PubMed:1718748).Curated1
Sequence conflicti409A → T in CAA43372 (PubMed:1718748).Curated1
Sequence conflicti476A → P in CAA43372 (PubMed:1718748).Curated1
Sequence conflicti478G → A in CAA43372 (PubMed:1718748).Curated1
Sequence conflicti478G → S in AAA36539 (PubMed:1851997).Curated1
Sequence conflicti478G → S in AAL55732 (PubMed:11508278).Curated1
Sequence conflicti478G → S in BAG36922 (PubMed:14702039).Curated1
Sequence conflicti478G → S in BAG70056 (PubMed:19054851).Curated1
Sequence conflicti478G → S in BAG70181 (PubMed:19054851).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05542217E → K in PROTEUSS and breast cancer; also detected in colorectal and ovarian cancer; somatic mutation; results in increased phosphorylation at T-308 and higher basal ubiquitination; the mutant protein is more efficiently recruited to the plasma membrane; alters phosphatidylinositiol phosphates lipid specificity of the AKT1 PH domain. 4 PublicationsCorresponds to variant dbSNP:rs121434592EnsemblClinVar.1
Natural variantiVAR_06979125R → C in CWS6. 1 PublicationCorresponds to variant dbSNP:rs397514644EnsemblClinVar.1
Natural variantiVAR_051617167V → A. Corresponds to variant dbSNP:rs11555433Ensembl.1
Natural variantiVAR_069792435T → P in CWS6. 1 PublicationCorresponds to variant dbSNP:rs397514645EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0561801 – 62Missing in isoform 2. 1 PublicationAdd BLAST62

Sequence databases

Select the link destinations:

EMBL nucleotide seque