Details for: PRKAB2

Gene ID: 5565

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PRKAB2

Ensembl ID: ENSG00000131791

Description: protein kinase AMP-activated non-catalytic subunit beta 2

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • chondrocyte CL0000138
    CSI 12.38
    rCSI 19.7%
    PRS 81.87
  • basal cell of epidermis CL0002187
    CSI 12
    rCSI 21.28%
    PRS 57.5
  • melanocyte of skin CL1000458
    CSI 10.18
    rCSI 13.87%
    PRS 56.47
  • suprabasal keratinocyte CL4033013
    CSI 5.13
    rCSI 8.37%
    PRS 56.44
  • fibroblast of lung CL0002553
    CSI 4.03
    rCSI 3.75%
    PRS 88.41
  • centrilobular region hepatocyte CL0019029
    CSI 3.95
    rCSI 10.31%
    PRS 84.11
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.7
    rCSI 3.34%
    PRS 86
  • midzonal region hepatocyte CL0019028
    CSI 3.44
    rCSI 8.08%
    PRS 85.68
  • interneuron CL0000099
    CSI 3.35
    rCSI 6.72%
    PRS 80.04
  • melanocyte CL0000148
    CSI 3.3
    rCSI 2.44%
    PRS 82.63
  • stem cell CL0000034
    CSI 3.23
    rCSI 3.11%
    PRS 82.43
  • megakaryocyte CL0000556
    CSI 3.19
    rCSI 13.82%
    PRS 89.91
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.17
    rCSI 7.11%
    PRS 73.06
  • goblet cell CL0000160
    CSI 2.92
    rCSI 2.76%
    PRS 85.42
  • mesodermal cell CL0000222
    CSI 2.91
    rCSI 3.49%
    PRS 85.89
  • hepatic stellate cell CL0000632
    CSI 2.9
    rCSI 10.86%
    PRS 81.63
  • colon epithelial cell CL0011108
    CSI 2.62
    rCSI 2.75%
    PRS 84.86
  • neural crest cell CL0011012
    CSI 2.47
    rCSI 1.95%
    PRS 78.79
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.45
    rCSI 4.32%
    PRS 71.78
  • renal alpha-intercalated cell CL0005011
    CSI 2.4
    rCSI 3.21%
    PRS 91.44
  • cerebral cortex endothelial cell CL1001602
    CSI 2.34
    rCSI 4.05%
    PRS 80.85
  • muscle cell CL0000187
    CSI 2.19
    rCSI 4.5%
    PRS 91.96
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.19
    rCSI 3.68%
    PRS 72.32
  • vascular leptomeningeal cell CL4023051
    CSI 2.16
    rCSI 3.79%
    PRS 82.73
  • extravillous trophoblast CL0008036
    CSI 2.14
    rCSI 2.65%
    PRS 85.76
  • VIP GABAergic cortical interneuron CL4023016
    CSI 2.1
    rCSI 2.51%
    PRS 72.46
  • colonocyte CL1000347
    CSI 2.04
    rCSI 2.93%
    PRS 86.36
  • hepatocyte CL0000182
    CSI 2.04
    rCSI 3.66%
    PRS 86.44
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.02
    rCSI 2.51%
    PRS 70.14
  • alveolar adventitial fibroblast CL4028006
    CSI 1.94
    rCSI 3.07%
    PRS 88.28
  • enterocyte CL0000584
    CSI 1.93
    rCSI 3.11%
    PRS 84.79
  • retinal cone cell CL0000573
    CSI 1.93
    rCSI 3.1%
    PRS 78.81
  • type B pancreatic cell CL0000169
    CSI 1.89
    rCSI 4.18%
    PRS 87.21
  • periportal region hepatocyte CL0019026
    CSI 1.83
    rCSI 7.11%
    PRS 85.08
  • BEST4+ enteroycte CL4030026
    CSI 1.82
    rCSI 2.26%
    PRS 87.38
  • intestinal tuft cell CL0019032
    CSI 1.74
    rCSI 2.66%
    PRS 89.74
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.72
    rCSI 2.21%
    PRS 73.47
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.52
    rCSI 3.85%
    PRS 79.78
  • cardiac muscle cell CL0000746
    CSI 1.36
    rCSI 1.95%
    PRS 78.63
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.31
    rCSI 2.1%
    PRS 73.49
  • placental villous trophoblast CL2000060
    CSI 1.28
    rCSI 1.97%
    PRS 86.02
  • blood vessel smooth muscle cell CL0019018
    CSI 1.11
    rCSI 9.05%
    PRS 83.41
  • GABAergic neuron CL0000617
    CSI 0.88
    rCSI 2.95%
    PRS 72.65
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 0.85
    rCSI 2.8%
    PRS 74.72
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.85
    rCSI 2.06%
    PRS 70.1
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.82
    rCSI 3.1%
    PRS 72.64
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.74
    rCSI 2.32%
    PRS 75.74
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.73
    rCSI 2.29%
    PRS 73.7
  • microcirculation associated smooth muscle cell CL0008035
    CSI 0.65
    rCSI 1.88%
    PRS 86.5
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.56
    rCSI 2.01%
    PRS 70.31
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.36
    rCSI 2.1%
    PRS 72.78

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PRKAB2](/details-gene/5565) (protein kinase AMP-activated non-catalytic subunit beta 2) is a protein-coding gene located on chromosome 1q21.1. It encodes the beta-2 subunit of the 5'-AMP-activated protein kinase (AMPK), a central metabolic sensor that plays a crucial role in regulating cellular energy homeostasis. As a non-catalytic subunit, PRKAB2 acts as a scaffold, bringing together the catalytic alpha and regulatory gamma subunits, and is essential for the stability and activity of the AMPK complex. **Overall**, expression data indicates that [PRKAB2](/details-gene/5565) is a significant gene in metabolically active or structurally demanding cell types, such as [chondrocytes](/details-cell/CL0000138), [basal cells of the epidermis](/details-cell/CL0002187), and [melanocytes of the skin](/details-cell/CL1000458), underscoring its fundamental role in cellular maintenance, growth, and response to energy stress. ## Cellular Roles and Expression Landscape The expression profile of [PRKAB2](/details-gene/5565) suggests a ubiquitous but highly regulated role in maintaining cellular function across diverse tissues. Its highest significance is observed in cells with high metabolic or biosynthetic demands. * **Structural and Proliferative Tissues:** The gene shows prominent significance in [chondrocytes](/details-cell/CL0000138) (CSI: 12.38) and various skin cells, including [basal cell of epidermis](/details-cell/CL0002187) (CSI: 12.00), [melanocyte of skin](/details-cell/CL1000458) (CSI: 10.18), and [suprabasal keratinocyte](/details-cell/CL4033013) (CSI: 5.13). This pattern suggests a critical role for AMPK-mediated energy sensing in processes like cartilage maintenance, skin barrier formation, and melanogenesis. * **Metabolic and Secretory Cells:** High significance in [centrilobular region hepatocytes](/details-cell/CL0019029) (CSI: 3.95) and [goblet cells](/details-cell/CL0000160) (CSI: 2.92) is consistent with AMPK's known function in regulating lipid and glucose metabolism in the liver and supporting the energy-intensive process of mucin production. * **Hematopoietic and Nervous Systems:** The gene is also notably active in progenitor cells like [megakaryocyte-erythroid progenitor cells](/details-cell/CL0000050) (CSI: 3.70) and mature [megakaryocytes](/details-cell/CL0000556) (CSI: 3.19), indicating its importance in platelet formation. Furthermore, its significance in neural cells such as [interneurons](/details-cell/CL0000099) (CSI: 3.35) and [astrocytes of the cerebral cortex](/details-cell/CL0002605) (CSI: 3.17) aligns with its involvement in neuronal energy homeostasis and synaptic transmission. Collectively, the broad but distinct expression landscape highlights [PRKAB2](/details-gene/5565) as a fundamental housekeeping gene essential for managing energy resources in cells with diverse physiological functions. ## Pathways and Molecular Function [PRKAB2](/details-gene/5565) is integral to the AMPK complex, which functions as a master regulator of cellular metabolism. Its involvement is central to numerous interconnected signaling pathways. * **Energy Metabolism:** As expected, [PRKAB2](/details-gene/5565) is a key component of pathways governing the '[Cellular response to nutrient levels](/details-ontology/GO:0031669)' and the '[Integration of energy metabolism](/details-pathway/R-HSA-163685)'. It participates in catabolic processes such as the '[Fatty acid biosynthetic process](/details-ontology/GO:0006633)' and '[Autophagy](/details-pathway/R-HSA-9612973)', while simultaneously inhibiting anabolic pathways like '[mTOR signalling](/details-pathway/R-HSA-165159)' via '[Energy dependent regulation of mTOR by LKB1-AMPK](/details-pathway/R-HSA-380972)'. This dual function allows cells to conserve energy during periods of metabolic stress. * **Signal Transduction and Transcription:** The gene's role extends beyond metabolism into core cellular signaling. It is involved in '[Signal transduction](/details-ontology/GO:0007165)' and pathways related to transcription, including '[Gene expression (transcription)](/details-pathway/R-HSA-74160)' and '[RNA polymerase II transcription](/details-pathway/R-HSA-73857)'. Notably, it is implicated in the '[Regulation of TP53 activity](/details-pathway/R-HSA-5633007)', suggesting a link between cellular energy status and the response to DNA damage or other cellular stresses. * **Neuronal Function:** In the nervous system, [PRKAB2](/details-gene/5565) is involved in '[Neuronal system](/details-pathway/R-HSA-112316)' pathways, specifically in '[Activation of NMDA receptors and postsynaptic events](/details-pathway/R-HSA-442755)'. This is consistent with its expression in neurons and astrocytes and points to a role for AMPK in modulating synaptic plasticity and neuronal survival in response to metabolic demands. ## Research Directions The central role of [PRKAB2](/details-gene/5565) in metabolic regulation makes it a compelling subject for research, particularly in the context of metabolic diseases and tissue homeostasis. ### Proposed Hypotheses 1. Given its high significance in [chondrocytes](/details-cell/CL0000138) and the known role of metabolic dysregulation in osteoarthritis, we hypothesize that diminished [PRKAB2](/details-gene/5565)-dependent AMPK activity in aging chondrocytes impairs their ability to manage oxidative stress and maintain extracellular matrix synthesis, thereby accelerating cartilage degradation. 2. Based on its association with Type 2 Diabetes Mellitus ([Link](https://pubmed.ncbi.nlm.nih.gov/12490143/)) and its role in '[Translocation of SLC2A4 (GLUT4) to the plasma membrane](/details-pathway/R-HSA-1445148)', we hypothesize that specific genetic variants in [PRKAB2](/details-gene/5565) lead to impaired insulin-stimulated glucose uptake in skeletal muscle and adipose tissue by disrupting the stability or localization of the AMPK complex. ### Key Experiments To test the first hypothesis regarding the role of [PRKAB2](/details-gene/5565) in chondrocyte health, a series of experiments could be conducted. One could use CRISPR/Cas9 to generate [PRKAB2](/details-gene/5565) knockout human induced pluripotent stem cells (iPSCs) and differentiate them into chondrocytes. These engineered chondrocytes would then be compared to isogenic controls. Key readouts would include metabolic profiling via Seahorse analysis to measure mitochondrial respiration and glycolysis, assessment of extracellular matrix production (e.g., aggrecan and collagen II) by qPCR and Western blot, and evaluation of the cellular response to pro-inflammatory cytokines like IL-1β to model arthritic conditions. ### Therapeutic Potential As a core component of the AMPK energy-sensing pathway, [PRKAB2](/details-gene/5565) represents a potential therapeutic target. Activation, rather than inhibition, of the AMPK pathway is a well-established strategy for treating metabolic disorders. Therefore, small molecule activators that either directly bind to the PRKAB2 subunit or promote the stability of the AMPK complex could have therapeutic value for conditions like type 2 diabetes, non-alcoholic fatty liver disease, and potentially age-related degenerative diseases. However, because AMPK is ubiquitously expressed and controls fundamental cellular processes, systemic activation could have significant off-target effects. The development of tissue-specific delivery mechanisms or compounds that selectively target AMPK complexes in metabolically stressed cells would be critical for translating this potential into safe and effective therapies.

Genular Protein ID: 891501067

Symbol: AAKB2_HUMAN

Name: 5'-AMP-activated protein kinase subunit beta-2

UniProtKB Accession Codes:

O43741 A8K9V5 B4DH06 Q5VXY0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CAZy 1 CCDS 1 CDD 1 CORUM 1 CTD 1 ChEMBL 1 ChiTaRS 1 ComplexPortal 6 DIP 1 DNASU 1 DisGeNET 1 DrugBank 4 EMBL 13 EMDB 3 Ensembl 1 EvolutionaryTrace 1 GO 10 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 17 PDBsum 17 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 10 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9575201

Title: Identification of a novel AMP-activated protein kinase beta subunit isoform that is highly expressed in skeletal muscle.

PubMed ID: 9575201

DOI: 10.1074/jbc.273.20.12443

PubMed ID: 12490143

Title: Variant screening of PRKAB2, a type 2 diabetes mellitus susceptibility candidate gene on 1q in Pima Indians.

PubMed ID: 12490143

DOI: 10.1006/mcpr.2002.0439

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 18691976

Title: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.

PubMed ID: 18691976

DOI: 10.1016/j.molcel.2008.07.007

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 18318008

Title: Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography.

PubMed ID: 18318008

DOI: 10.1002/pmic.200700884

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19369195

Title: Large-scale proteomics analysis of the human kinome.

PubMed ID: 19369195

DOI: 10.1074/mcp.m800588-mcp200

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21460634

Title: Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop.

PubMed ID: 21460634

DOI: 10.4161/auto.7.7.15451

PubMed ID: 17307971

Title: AMP-activated protein kinase in metabolic control and insulin signaling.

PubMed ID: 17307971

DOI: 10.1161/01.res.0000256090.42690.05

PubMed ID: 17712357

Title: AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy.

PubMed ID: 17712357

DOI: 10.1038/nrm2249

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 17851531

Title: Structural basis for AMP binding to mammalian AMP-activated protein kinase.

PubMed ID: 17851531

DOI: 10.1038/nature06161

PubMed ID: 21399626

Title: Structure of mammalian AMPK and its regulation by ADP.

PubMed ID: 21399626

DOI: 10.1038/nature09932

Sequence Information:

  • Length: 272
  • Mass: 30302
  • Checksum: 42B23BD70B92519C
  • Sequence:
    • MGNTTSDRVS GERHGAKAAR SEGAGGHAPG KEHKIMVGST DDPSVFSLPD SKLPGDKEFV 
SWQQDLEDSV KPTQQARPTV IRWSEGGKEV FISGSFNNWS TKIPLIKSHN DFVAILDLPE 
GEHQYKFFVD GQWVHDPSEP VVTSQLGTIN NLIHVKKSDF EVFDALKLDS MESSETSCRD 
LSSSPPGPYG QEMYAFRSEE RFKSPPILPP HLLQVILNKD TNISCDPALL PEPNHVMLNH 
LYALSIKDSV MVLSATHRYK KKYVTTLLYK PI