Creatine is a naturally occurring compound. It belongs to the class of organic compounds known as alpha amino acids and derivatives. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon), or a derivative thereof. Creatine is found in all vertebrates where it facilitates recycling of adenosine triphosphate (ATP). Its primary metabolic role is to combine with a phosphoryl group, via the enzyme creatine kinase, to generate phosphocreatine, which is used to regenerate ATP. Most of the human body’s total creatine and phosphocreatine stores are found in skeletal muscle (95%), while the remainder is distributed in the blood, brain, testes, and other tissues.

• • Chemical formula: C₄H₉N₃O₂
  • Monoisotopic Molecular Weight: 131.069476547
  • IUPAC name: 2-(N-methylcarbamimidamido)acetic acid
  • CAS Registry Number: 57-00-1
  • SMILES: CN(CC(O)=O)C(N)=N

• GC-MS spectra
  
  Spectrum type: Experimental GC-MS; Description; GC-MS Spectrum – Creatine GC-EI-TOF (Non-derivatized); Splash key: splash10-0002-0900000000-f89f340e776ae37776b3; Deposition date: 2018-05-18; Source: HMDB team, MONA, MassBank

• MS-MS spectra
  
  Spectrum type: Experimental LC-MS/MS; Description; LC-MS/MS Spectrum – Creatine Quattro_QQQ 40V, Positive-QTOF (Annotated); Splash key: splash10-0006-9000000000-13b7d28e8f5be1c5dada; Deposition date: 2012-07-24; Source: HMDB team, MONA

• NMR spectra
  
  Spectrum type: Experimental 1D NMR; Description; 1H NMR Spectrum (1D, 500 MHz, H2O, experimental); Deposition date: 2012-12-04; Source: Wishart Lab

• Cellular locations: Cytoplasm, Extracellular and Mitochondria
• Biospecimen Locations: Blood, Breast Milk, Cerebrospinal Fluid (CSF), Feces, Saliva, Sweat, Urine.
• Tissue locations: Adipose Tissue, Bladder, Brain, Epidermis, Fibroblasts, Heart, Intestine, Kidney, Neuron, Placenta, Platelet, Prostate, Skeletal Muscle, Spleen, Testis

• Glycine amidinotransferase
  • General function: Amino acid transport and metabolism
  • Gene Name: GATM
  • Uniprot ID: P50440
  • Molecular weight: 48455.01
• Guanidinoacetate N-methyltransferase
  • General function: Involved in guanidinoacetate N-methyltransferase activity
  • Gene Name: GAMT
  • Uniprot ID: Q14353
  • Molecular weight: 26317.925
• Creatine kinase S-type, mitochondrial
  • General function: Involved in kinase activity
  • Gene Name: CKMT2
  • Uniprot ID: P17540
  • Molecular weight: 47504.08
• Creatine kinase U-type, mitochondrial
  • General function: Involved in kinase activity
  • Gene Name: CKMT1A
  • Uniprot ID: P12532
  • Molecular weight: 47036.3
• Creatine kinase B-type
  • General function: Involved in kinase activity
  • Gene Name: CKB
  • Uniprot ID: P12277
  • Molecular weight: 42643.95
• Creatine kinase M-type
  • General function: Involved in kinase activity
  • Gene Name: CKM
  • Uniprot ID: P06732
  • Molecular weight: 43100.91
• Solute carrier family 6 member 8
  • General function: Involved in neurotransmitter:sodium symporter activity
  • Gene Name: SLC6A8
  • Uniprot ID: P48029
  • Molecular weight: 69483.91
• Solute carrier family 22 member 5
  • General function: Involved in ion transmembrane transporter activity. A creatine efflux transporter in oligodendrocytes
  • Gene Name: SLC22A5
  • Uniprot ID: O76082

Phosphocreatine, also known as phosphorylcreatine or creatine phosphate (PCr), is a phosphorylated creatine molecule that serves as a rapidly mobilizable reserve of high-energy phosphates in skeletal muscle, myocardium and the brain to recycle adenosine triphosphate, the energy currency of the cell. Phosphocreatine undergoes irreversible cyclization and dehydration to form creatinine at a fractional rate of 0.026 per day, thus forming approximately 2 g creatinine/day in an adult male. This is the amount of creatine that must be provided either from dietary sources or by endogenous synthesis to maintain the body pool of (creatine and) phosphocreatine.

• • Chemical formula: C₄H₁₀N₃O₅P
  • Monoisotopic Molecular Weight: 211.035806957
  • IUPAC name: 2-(N-methyl-N’-phosphonocarbamimidamido)acetic acid
  • CAS Registry Number: 67-07-2
  • SMILES: CN(CC(O)=O)C(=N)NP(O)(O)=O

• MS-MS spectra
  
  Spectrum type: Experimental LC-MS/MS; Description; LC-MS/MS Spectrum – Phosphocreatine Quattro_QQQ 40V, Positive-QTOF (Annotated); Splash key: splash10-004i-9000000000-0b9440fbeacd93f8e2c6; Deposition date: 2012-07-24; Source: HMDB team, MONA
  

• NMR spectra
  
  Spectrum type: Experimental 1D NMR; Description; 1H NMR Spectrum (1D, 500 MHz, H2O, experimental); Deposition date: 2012-12-04; Source: Wishart Lab
  

• Cellular locations: Cytoplasm, Extracellular and Mitochondria
• Biospecimen Locations: Blood, Breast Milk, Urine.
• Tissue locations: Adipose Tissue, Basal Ganglia, Brain, Epidermis, Fibroblasts, Kidney, Neuron, Placenta, Skeletal Muscle, Testis

• Creatine kinase S-type, mitochondrial
  • General function: Involved in kinase activity
  • Gene Name: CKMT2
  • Uniprot ID: P17540
  • Molecular weight: 47504.08
• Creatine kinase U-type, mitochondrial
  • General function: Involved in kinase activity
  • Gene Name: CKMT1A
  • Uniprot ID: P12532
  • Molecular weight: 47036.3
• Creatine kinase B-type
  • General function: Involved in kinase activity
  • Gene Name: CKB
  • Uniprot ID: P12277
  • Molecular weight: 42643.95
• Creatine kinase M-type
  • General function: Involved in kinase activity
  • Gene Name: CKM
  • Uniprot ID: P06732
  • Molecular weight: 43100.91

Creatinine or creatine anhydride is a member of the class of compounds known as imidazolidinones. Imidazolidinones are a class of 5-membered ring heterocycles structurally related to imidazole. Creatinine can also be classified as an amino acid derivative.  Creatinine arises from the production of creatine. In particular, the loss of a water molecule from creatine results in the formation of creatinine. Creatinine is transferred to the kidneys by blood plasma, whereupon it is eliminated from the body by glomerular filtration and partial tubular excretion. Creatinine is usually produced at a fairly constant rate by the body, which is roughly proportional to muscle mass and body size

• • Chemical formula: C₄H₇N₃O
  • Monoisotopic Molecular Weight: 113.058911861
  • IUPAC name: 2-imino-1-methylimidazolidin-4-one
  • CAS Registry Number: 60-27-5
  • SMILES: CN1CC(=O)NC1=N

• MS-MS spectra
  
  Spectrum type: Experimental GC-MS; Description; GC-MS Spectrum – Creatinine GC-MS (Non-derivatized); Splash key: splash10-014i-0901000000-bd882951c92733ecbc9e; Deposition date: 2017-09-12; Source: HMDB team, MONA, MassBank
  

• NMR spectra
  
  Spectrum type: Experimental LC-MS/MS Spectrum – Creatinine Quattro_QQQ 40V, Positive-QTOF (Annotated); Splash key: splash10-0006-9000000000-bfa35af1a437cbc8b5ec; Deposition date: 2012-07-24; Source: HMDB team, MONA
  

• Cellular locations: Cytoplasm
• Biospecimen Locations: Amniotic Fluid, Blood, Breast Milk, Cerebrospinal Fluid (CSF), Feces, Saliva, Sweat, Urine
• Tissue locations: Adipose Tissue, Bladder, Fibroblasts, Kidney, Liver, Neuron, Pancreas, Placenta, Platelet, Prostate, Skeletal Muscle, Spleen, Testis, Thyroid Gland

• Description: Glycine amidinotransferase
• Tissue specificity (RNA): Group enriched (Kidney, Liver, Pancreas)
• Tau specificity score (RNA):  0.55
• Protein evidence: Evidence at protein level
• Protein expression: Granular cytoplasmic expression in several different tissue types, mainly in kidney, liver and pancreas.
• Data reliability description: Medium consistency between antibody staining and RNA expression data.
• Reliability score: Enhanced
• Antibodies: HPA026077

• Description: Guanidinoacetate N-methyltransferase
• Tissue specificity (RNA): Tissue enhanced (Liver, Skeletal muscle, Tongue)
• Tau specificity score (RNA):  0.52
• Protein evidence: Evidence at protein level
• Protein expression:    Cytoplasmic and membranous expression in several tissues.
• Data reliability description: Low consistency between antibody staining and RNA expression data.
• Reliability score: Approved
• Antibodies: HPA051806

• Description: Creatine kinase B
• Tissue specificity (RNA): Tissue enhanced (Brain)
• Tau specificity score (RNA):  0.36
• Protein evidence: Evidence at protein level
• Protein expression: Cytoplasmic expression in parietal cells in stomach, and cells in the CNS.
• Data reliability description: High consistency between antibody staining and RNA expression data.
• Reliability score: Enhanced
• Antibodies: HPA001254 , CAB047313

• Description: Creatine kinase, M-type
• Tissue specificity (RNA): Group enriched (Skeletal muscle, Tongue)
• Tau specificity score (RNA):  0.81
• Protein evidence: Evidence at protein level
• Protein expression: Cytoplasmic expression in skeletal muscle and heart.
• Data reliability description: High consistency between antibody staining and RNA expression data.
• Reliability score: Enhanced
• Antibodies: HPA047859

• Description: Creatine kinase, mitochondrial 1A
• Tissue specificity (RNA): Tissue enhanced (Brain, Esophagus, Intestine)
• Tau specificity score (RNA):  0.59
• Protein evidence: Evidence at protein level
• Protein expression: Granular cytoplasmic expression in several different tissue types, mainly in gastrointestinal tract and squamous epithelium.
• Data reliability description: Low consistency between antibody staining and RNA expression data. Caution, targets protein from more than one gene. Presumed off target binding observed and disregarded.
• Reliability score: Uncertain
• Antibodies: HPA043491

• Description: Creatine kinase, mitochondrial 1B
• Tissue specificity (RNA): Tissue enhanced (Brain, Esophagus, Intestine)
• Tau specificity score (RNA):  0.62
• Protein evidence: Evidence at protein level
• Protein expression: Granular cytoplasmic expression in several different tissue types, mainly in gastrointestinal tract and squamous epithelium.
• Data reliability description: Low consistency between antibody staining and RNA expression data. Caution, targets protein from more than one gene. Presumed off target binding observed and disregarded.
• Reliability score: Uncertain
• Antibodies: HPA043491

• Description: Creatine kinase, mitochondrial 2
• Tissue specificity (RNA): Group enriched (Heart muscle, Skeletal muscle, Tongue)
• Tau specificity score (RNA):  0.69
• Protein evidence: Evidence at protein level
• Protein expression: Cytoplasmic expression mainly in heart and skeletal muscle..
• Data reliability description: Medium consistency between antibody staining and RNA expression data. Presumed off target binding observed and disregarded.
• Reliability score: Enhanced
• Antibodies: HPA051880

• Description: Solute carrier family 6 member 8
• Tissue specificity (RNA): Low tissue specificity
• Tau specificity score (RNA):  0.33
• Protein evidence: Detected in all
• Reliability score: Pending normal tissue annotation.

This combines enrichment analysis with a knowledge graph data representation to query a large collection of processed datasets made of associations between genes and many biological and biomedical terms. This is an extension of the popular gene set enrichment analysis tool Enrichr, designed to enhance the integration and visualization of enrichment results across multiple gene set libraries and domains of knowledge (available at: https://maayanlab.cloud/enrichr-kg).

The permanent link below provides access to enrichment analysis using the classical Enrichr tool, covering diverse categories such as Transcription, Pathways, Ontologies, Diseases/Drugs, Cell Types, Misc, Legacy, and Crowd. Use it to explore and extract detailed insights across these domains:

GENE SET ENRICHMENT ANALYSIS

References:

• Evangelista JE, Xie Z, Marino GB, Nguyen N, Clarke DJB, Ma’ayan A. Enrichr-KG: bridging enrichment analysis across multiple libraries. Nucleic Acids Res. 2023 May 11:gkad393. https://doi.org/10.1093/nar/gkad393
• Chen, E. Y., Tan, C. M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G. V., Clark, N. R., & Ma’ayan, A. (2013). Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC bioinformatics, 14, 128. https://doi.org/10.1186/1471-2105-14-128
• Kuleshov, M. V., Jones, M. R., Rouillard, A. D., Fernandez, N. F., Duan, Q., Wang, Z., Koplev, S., Jenkins, S. L., Jagodnik, K. M., Lachmann, A., McDermott, M. G., Monteiro, C. D., Gundersen, G. W., & Ma’ayan, A. (2016). Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic acids research, 44(W1), W90–W97. https://doi.org/10.1093/nar/gkw377 
• Xie, Z., Bailey, A., Kuleshov, M. V., Clarke, D. J., Evangelista, J. E., Jenkins, S. L., … & Ma’ayan, A. (2021). Gene set knowledge discovery with Enrichr. Current protocols, 1(3), e90. https://doi.org/10.1002/cpz1.90

Protein-protein interactions network of creatine metabolism. The prioritized gene/proteins identified in the manual curation were submitted to the Search Tool for the Retrieval of Interacting Genes (STRING, https://string-db.org/). The colored nodes represent the results of the Markov cluster algorithm to group proteins. The colors of interactions correspond to: known from curated databases (cyan), experimentally determined (purple); predicted interactions based on gene neighborhood (green), gene fusions (red), and gene co-occurrence (dark blue); and others, such as text-mining (yellow), co-expression (black), and protein homology (light blue).

The network is available at https://version-12-0.string-db.org/cgi/network?networkId=bwu8z9Urdb75.

STRING is a Core Data Resource as designated by Global Biodata Coalition and ELIXIR.

The DIANA-microT 2023 webserver is a computational tool developed by the DIANA Lab that predicts and archives miRNA-mRNA interactions (available at: https://dianalab.e-ce.uth.gr/microt_webserver/#/interactions). It uses the DIANA-microT-CDS algorithm to analyze miRNA sequences and their interactions with protein-coding genes, hosting over 86 million predicted interactions across six species. It also includes predictions for viral miRNAs targeting host transcripts. This resource aids in understanding miRNA roles in gene regulation and disease, integrating data from various biological levels for comprehensive analysis.

The gene list of creatine metabolism-related genes (GAMT, GATM, CKB, CKM, CKMT1B, CKMT1A, CKMT2, SLC6A8, and SLC6A10P) was used as input data, with an interaction score threshold of 0.7, human as species, and high miRNA confidence settings.

Reference:

• Tastsoglou, S., Alexiou, A., Karagkouni, D., Skoufos, G., Zacharopoulou, E., & Hatzigeorgiou, A. G. (2023). DIANA-microT 2023: including predicted targets of virally encoded miRNAs. Nucleic acids research, 51(W1), W148–W153. https://doi.org/10.1093/nar/gkad283
• The “ELIXIR-GR: Managing and Analysing Life Sciences Data (MIS: 5002780)” Project is co-financed by Greece and the European Union – European Regional Development Fund