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Record Information
Version2.0
Creation Date2014-08-29 05:48:38 UTC
Update Date2014-12-24 20:26:40 UTC
Accession NumberT3D4166
Identification
Common NameSpermine
ClassSmall Molecule
DescriptionSpermine is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure. [PubChem]
Compound Type
  • Amine
  • Dietary Supplement
  • Drug
  • Food Toxin
  • Metabolite
  • Micronutrient
  • Natural Compound
  • Nutraceutical
  • Organic Compound
  • Supplement
  • Uremic Toxin
Chemical Structure
Thumb
Synonyms
Synonym
1,5,10,14-Tetraazatetradecane
4,9-Diaza-1,12-dodecanediamine
4,9-Diazadodecamethylenediamine
4,9-Diazadodecane-1,12-diamine
Diaminopropyl-tetramethylenediamine
Diaminopropyltetramethylenediamine
Gerontine
Musculamine
N,N'-Bis(3-aminopropyl)-1,4-Butanediamine
N,N'-Bis(3-aminopropyl)-1,4-tetramethylenediamine
N,N'-Bis(3-aminopropyl)butane-1,4-diamine
N1,N4-bis(3-aminopropyl)-1,4-butanediamine
Neuridine
Spermin
Spermine dihydrate
Spermine puriss
SPM
Chemical FormulaC10H26N4
Average Molecular Mass202.340 g/mol
Monoisotopic Mass202.216 g/mol
CAS Registry Number71-44-3
IUPAC Name(3-aminopropyl)({4-[(3-aminopropyl)amino]butyl})amine
Traditional Namespermine
SMILESNCCCNCCCCNCCCN
InChI IdentifierInChI=1S/C10H26N4/c11-5-3-9-13-7-1-2-8-14-10-4-6-12/h13-14H,1-12H2
InChI KeyInChIKey=PFNFFQXMRSDOHW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dialkylamines. These are organic compounds containing a dialkylamine group, characterized by two alkyl groups bonded to the amino nitrogen.
KingdomOrganic compounds
Super ClassOrganic nitrogen compounds
ClassOrganonitrogen compounds
Sub ClassAmines
Direct ParentDialkylamines
Alternative Parents
Substituents
  • Secondary aliphatic amine
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Primary amine
  • Primary aliphatic amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Brain
  • Erythrocyte
  • Fibroblasts
  • Intestine
  • Liver
  • Muscle
  • Neuron
  • Pancreas
  • Platelet
  • Prostate
  • Skin
  • Testes
Pathways
NameSMPDB LinkKEGG Link
Spermidine and Spermine BiosynthesisSMP00445 Not Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point29°C
Boiling Point150-150°C
Solubility> 100 mg/mL
LogP-0.7
Predicted Properties
PropertyValueSource
Water Solubility2.19 g/LALOGPS
logP-0.66ALOGPS
logP-1.5ChemAxon
logS-2ALOGPS
pKa (Strongest Basic)10.8ChemAxon
Physiological Charge4ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area76.1 ŲChemAxon
Rotatable Bond Count11ChemAxon
Refractivity62.56 m³·mol⁻¹ChemAxon
Polarizability26.69 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (x TMS)splash10-014u-1900000000-e9620319823eaecceccc2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (x TMS)splash10-00s6-3900000000-d7da5cd1c0be289412ee2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (Non-derivatized)splash10-00r6-1900000000-861e0541e2eb67219b932014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (5 TMS)splash10-00di-7900000000-9706a16d903df3f9e0942014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (5 TMS)splash10-00di-5900000000-eb1574dc4aea2972932b2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (5 TMS)splash10-00ei-8900000000-710d44c573ed398f7db92014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (5 TMS)splash10-00s6-3900000000-cb82c1371fa767015cff2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (6 TMS)splash10-00rf-1900000000-ca3a2df44acb740134cd2014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-MS (6 TMS)splash10-00y0-1900000000-7ba8e67861945901b3812014-06-16View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-014u-1900000000-e9620319823eaecceccc2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00s6-3900000000-d7da5cd1c0be289412ee2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00r6-1900000000-861e0541e2eb67219b932017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00di-7900000000-9706a16d903df3f9e0942017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00di-5900000000-eb1574dc4aea2972932b2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00ei-8900000000-710d44c573ed398f7db92017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00s6-3900000000-cb82c1371fa767015cff2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00rf-1900000000-ca3a2df44acb740134cd2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00y0-1900000000-7ba8e67861945901b3812017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-01bl-1900000000-5a4875c4cf337f0cff9c2017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000i-7900000000-4e66988ec8e890a03e132017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00rf-2900000000-9d5a63fbbd1662e5dc432017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-01w1-4900000000-f7c07f1cee7101fc31d72017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-053r-9300000000-2ce22d19e72f10b80f342016-09-22View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0w29-2940000000-a8b05c7cfaea58c5d82d2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-03di-1900000000-75ac3953e5378c465a622012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-001i-9000000000-e3b84db5723912be8a4f2012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0udi-0930000000-4bb02118dea11e2101f82012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0006-9000000000-468357ae06dea8985d852012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-00b9-6900000000-cf244bbfdbb5b7889d7a2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-004i-0900000000-c5af077deeab934c36b72012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0udi-0940000000-098121f449eb29dd74be2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-0006-9000000000-167ef7503b0827eb212f2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-03di-0900000000-feb04e188e675948f7952012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT (LTQ Orbitrap XL, Thermo Scientfic) , Positivesplash10-004i-0900000000-93e15f4592fe9bbeb3672012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-0udi-0090000000-c22e98adb3dc62b1eb772012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-01t9-0900000000-76aa5e4bf523c2027cba2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-03di-4900000000-b762c20d8a09a78cf9312012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-001i-9300000000-0428cb6df2b593ded5672012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-001i-9000000000-c319f927047d78e2b69b2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positivesplash10-004i-0900000000-b4f106f6fe26766fbf732012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positivesplash10-03di-0900000000-29d4a223bb44ded927b52012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positivesplash10-01q9-9500000000-d1b7e914e9ccee2d0f662012-08-31View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udr-2970000000-268b93360fb5eaa19e492015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a73-9810000000-ee919f22493191f567082015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4l-9200000000-f7cb18a7a6036554cb6b2015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0090000000-ea2e2f233958fa61cd8b2015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-3390000000-0ade7d389047531a84ee2015-05-27View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05fu-9200000000-e760ec8b3259e54992ce2015-05-27View Spectrum
MSMass Spectrum (Electron Ionization)splash10-053u-9100000000-5a106273203d28e4a7012014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR1H NMR Spectrum (1D, D2O, experimental)Not Available2016-10-22View Spectrum
1D NMR13C NMR Spectrum (1D, D2O, experimental)Not Available2016-10-22View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
2D NMR[1H, 1H]-TOCSY. Unexported temporarily by An Chi on Oct 15, 2021 until json or nmrML file is generated. 2D NMR Spectrum (experimental)Not Available2012-12-04View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureEndogenous, Ingestion, Dermal (contact)
Mechanism of ToxicityUremic toxins such as spermine are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (2). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (3). Spermine is derived from spermidine by spermine synthase. Spermine is a polyamine, a small organic cations that is absolutely required for eukaryotic cell growth. Spermine, is normally found in millimolar concentrations in the nucleus. Spermine functions directly as a free radical scavenger, and forms a variety of adducts that prevent oxidative damage to DNA. Oxidative damage to DNA by reactive oxygen species is a continual problem that cells must guard against to survive. Hence, spermine is a major natural intracellular compound capable of protecting DNA from free radical attack. Spermine is also implicated in the regulation of gene expression, the stabilization of chromatin, and the prevention of endonuclease-mediated DNA fragmentation.
MetabolismUremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor nutritional supplementation, also for treating dietary shortage or imbalance
Minimum Risk LevelNot Available
Health EffectsChronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
SymptomsAs a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.
TreatmentKidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00127
HMDB IDHMDB01256
PubChem Compound ID1103
ChEMBL IDCHEMBL23194
ChemSpider ID1072
KEGG IDC00750
UniProt IDNot Available
OMIM ID
ChEBI ID15746
BioCyc IDSPERMINE
CTD IDNot Available
Stitch IDNot Available
PDB IDSPM
ACToR IDNot Available
Wikipedia LinkSpermine
References
Synthesis Reference

Koji Nakanishi, Amira T. Eldefrawi, Mohyee E. Eldefrawi, Peter N. R. Usherwood, “Butyryl-tyrosinyl spermine, analogs thereof and methods of preparing and using same.” U.S. Patent US5770625, issued January, 1966.

MSDSLink
General References
  1. Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A: Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012 Jul;23(7):1258-70. doi: 10.1681/ASN.2011121175. Epub 2012 May 24. [22626821 ]
  2. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  3. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
  4. Mollica F, Li Volti S, Rapisarda A, Longo G, Pavone L, Vanella A: Increased erythrocytic spermine in Duchenne muscular dystrophy. Pediatr Res. 1980 Nov;14(11):1196-8. [7454431 ]
  5. Swift TA, Dias JA: Effects of the polyamine spermine on binding of follicle-stimulating hormone to membrane-bound immature bovine testis receptors. Biochim Biophys Acta. 1986 Feb 21;885(2):221-30. [3004602 ]
  6. Cipolla BG, Ziade J, Bansard JY, Moulinoux JP, Staerman F, Quemener V, Lobel B, Guille F: Pretherapeutic erythrocyte polyamine spermine levels discriminate high risk relapsing patients with M1 prostate carcinoma. Cancer. 1996 Sep 1;78(5):1055-65. [8780544 ]
  7. Venza M, Visalli M, Cicciu D, Teti D: Determination of polyamines in human saliva by high-performance liquid chromatography with fluorescence detection. J Chromatogr B Biomed Sci Appl. 2001 Jun 5;757(1):111-7. [11419735 ]
  8. Uehara N, Shirakawa S, Uchino H, Saeki Y: Elevated contents of spermidine and spermine in the erythrocytes of cancer patients. Cancer. 1980 Jan 1;45(1):108-11. [7350997 ]
  9. Jensen PK, Therkelsen AJ: Selective inhibition of fibroblasts by spermine in primary cultures of normal human skin epithelial cells. In Vitro. 1982 Oct;18(10):867-71. [7173947 ]
  10. Loser C, Folsch UR, Paprotny C, Creutzfeldt W: Polyamines in colorectal cancer. Evaluation of polyamine concentrations in the colon tissue, serum, and urine of 50 patients with colorectal cancer. Cancer. 1990 Feb 15;65(4):958-66. [2297664 ]
  11. Proctor MS, Fletcher HV Jr, Shukla JB, Rennert OM: Elevated spermidine and spermine levels in the blood of psoriasis patients. J Invest Dermatol. 1975 Oct;65(4):409-11. [1176793 ]
  12. Lorenz B, Francis F, Gempel K, Boddrich A, Josten M, Schmahl W, Schmidt J, Lehrach H, Meitinger T, Strom TM: Spermine deficiency in Gy mice caused by deletion of the spermine synthase gene. Hum Mol Genet. 1998 Mar;7(3):541-7. [9467015 ]
  13. Hosseinkhani H, Azzam T, Tabata Y, Domb AJ: Dextran-spermine polycation: an efficient nonviral vector for in vitro and in vivo gene transfection. Gene Ther. 2004 Jan;11(2):194-203. [14712304 ]
  14. El Baze P, Milano G, Verrando P, Renee N, Ortonne JP: Polyamine levels in normal human skin. A comparative study of pure epidermis, pure dermis, and suction blister fluid. Arch Dermatol Res. 1983;275(4):218-21. [6625645 ]
  15. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [19212411 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Spermine synthase activity
Specific Function:
Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM).
Gene Name:
SMS
Uniprot ID:
P52788
Molecular Weight:
41267.855 Da
References
  1. Lopatin AN, Shantz LM, Mackintosh CA, Nichols CG, Pegg AE: Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis. J Mol Cell Cardiol. 2000 Nov;32(11):2007-24. [11040105 ]
  2. Korhonen VP, Niiranen K, Halmekyto M, Pietila M, Diegelman P, Parkkinen JJ, Eloranta T, Porter CW, Alhonen L, Janne J: Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs. Mol Pharmacol. 2001 Feb;59(2):231-8. [11160858 ]
  3. Cason AL, Ikeguchi Y, Skinner C, Wood TC, Holden KR, Lubs HA, Martinez F, Simensen RJ, Stevenson RE, Pegg AE, Schwartz CE: X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Hum Genet. 2003 Dec;11(12):937-44. [14508504 ]
  4. Wang X, Ikeguchi Y, McCloskey DE, Nelson P, Pegg AE: Spermine synthesis is required for normal viability, growth, and fertility in the mouse. J Biol Chem. 2004 Dec 3;279(49):51370-5. Epub 2004 Sep 30. [15459188 ]
  5. Schwartz CE, Wang X, Stevenson RE, Pegg AE: Spermine synthase deficiency resulting in X-linked intellectual disability (Snyder-Robinson syndrome). Methods Mol Biol. 2011;720:437-45. doi: 10.1007/978-1-61779-034-8_28. [21318891 ]
  6. Wang X, Pegg AE: Use of (Gyro) Gy and spermine synthase transgenic mice to study functions of spermine. Methods Mol Biol. 2011;720:159-70. doi: 10.1007/978-1-61779-034-8_9. [21318872 ]
  7. Theiss C, Bohley P, Voigt J: Regulation by polyamines of ornithine decarboxylase activity and cell division in the unicellular green alga Chlamydomonas reinhardtii. Plant Physiol. 2002 Apr;128(4):1470-9. [11950995 ]
  8. Krauss M, Langnaese K, Richter K, Brunk I, Wieske M, Ahnert-Hilger G, Veh RW, Laube G: Spermidine synthase is prominently expressed in the striatal patch compartment and in putative interneurones of the matrix compartment. J Neurochem. 2006 Apr;97(1):174-89. Epub 2006 Mar 3. [16515550 ]
  9. Kobayashi M, Takao K, Shiota Y, Sugita Y, Takahashi M, Nakae D, Samejima K: Inhibition of putrescine aminopropyltransferase influences rat liver regeneration. Biol Pharm Bull. 2006 May;29(5):863-7. [16651710 ]
  10. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  11. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Protein homodimerization activity
Specific Function:
Key enzyme of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine.
Gene Name:
ODC1
Uniprot ID:
P11926
Molecular Weight:
51147.73 Da
References
  1. Nilsson J, Grahn B, Heby O: Antizyme inhibitor is rapidly induced in growth-stimulated mouse fibroblasts and releases ornithine decarboxylase from antizyme suppression. Biochem J. 2000 Mar 15;346 Pt 3:699-704. [10698696 ]
  2. Ray RM, Viar MJ, Yuan Q, Johnson LR: Polyamine depletion delays apoptosis of rat intestinal epithelial cells. Am J Physiol Cell Physiol. 2000 Mar;278(3):C480-9. [10712236 ]
  3. Korhonen VP, Niiranen K, Halmekyto M, Pietila M, Diegelman P, Parkkinen JJ, Eloranta T, Porter CW, Alhonen L, Janne J: Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs. Mol Pharmacol. 2001 Feb;59(2):231-8. [11160858 ]
  4. Rohn G, Els T, Hell K, Ernestus RI: Regional distribution of ornithine decarboxylase activity and polyamine levels in experimental cat brain tumors. Neurochem Int. 2001 Aug;39(2):135-40. [11408092 ]
  5. Ernestus RI, Rohn G, Schroder R, Els T, Klekner A, Paschen W, Klug N: Polyamine metabolism in brain tumours: diagnostic relevance of quantitative biochemistry. J Neurol Neurosurg Psychiatry. 2001 Jul;71(1):88-92. [11413269 ]
  6. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  7. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Spermine:oxygen oxidoreductase (spermidine-forming) activity
Specific Function:
Flavoenzyme which catalyzes the oxidation of spermine to spermidine. Can also use N(1)-acetylspermine and spermidine as substrates, with different affinity depending on the isoform (isozyme) and on the experimental conditions. Plays an important role in the regulation of polyamine intracellular concentration and has the potential to act as a determinant of cellular sensitivity to the antitumor polyamine analogs. May contribute to beta-alanine production via aldehyde dehydrogenase conversion of 3-amino-propanal.
Gene Name:
SMOX
Uniprot ID:
Q9NWM0
Molecular Weight:
61818.76 Da
References
  1. Binda C, Angelini R, Federico R, Ascenzi P, Mattevi A: Structural bases for inhibitor binding and catalysis in polyamine oxidase. Biochemistry. 2001 Mar 6;40(9):2766-76. [11258887 ]
  2. Vujcic S, Diegelman P, Bacchi CJ, Kramer DL, Porter CW: Identification and characterization of a novel flavin-containing spermine oxidase of mammalian cell origin. Biochem J. 2002 Nov 1;367(Pt 3):665-75. [12141946 ]
  3. Vujcic S, Liang P, Diegelman P, Kramer DL, Porter CW: Genomic identification and biochemical characterization of the mammalian polyamine oxidase involved in polyamine back-conversion. Biochem J. 2003 Feb 15;370(Pt 1):19-28. [12477380 ]
  4. Wang Y, Murray-Stewart T, Devereux W, Hacker A, Frydman B, Woster PM, Casero RA Jr: Properties of purified recombinant human polyamine oxidase, PAOh1/SMO. Biochem Biophys Res Commun. 2003 May 16;304(4):605-11. [12727196 ]
  5. Bacchi CJ, Rattendi D, Faciane E, Yarlett N, Weiss LM, Frydman B, Woster P, Wei B, Marton LJ, Wittner M: Polyamine metabolism in a member of the phylum Microspora (Encephalitozoon cuniculi): effects of polyamine analogues. Microbiology. 2004 May;150(Pt 5):1215-24. [15133083 ]
  6. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  7. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
4. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Trubetskoy VS, Wolff JA, Budker VG: The role of a microscopic colloidally stabilized phase in solubilizing oligoamine-condensed DNA complexes. Biophys J. 2003 Feb;84(2 Pt 1):1124-30. [12547793 ]
  2. Cho SK, Kwon YJ: Polyamine/DNA polyplexes with acid-degradable polymeric shell as structurally and functionally virus-mimicking nonviral vectors. J Control Release. 2011 Mar 30;150(3):287-97. doi: 10.1016/j.jconrel.2010.12.004. Epub 2010 Dec 16. [21167887 ]
  3. Saminathan M, Thomas T, Shirahata A, Pillai CK, Thomas TJ: Polyamine structural effects on the induction and stabilization of liquid crystalline DNA: potential applications to DNA packaging, gene therapy and polyamine therapeutics. Nucleic Acids Res. 2002 Sep 1;30(17):3722-31. [12202757 ]
  4. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  5. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular Weight:
28870.0 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory231 uMNot AvailableBindingDB 50009369
References
  1. Carta F, Temperini C, Innocenti A, Scozzafava A, Kaila K, Supuran CT: Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22. doi: 10.1021/jm1003667. [20590092 ]
  2. Durdagi S, Senturk M, Ekinci D, Balaydin HT, Goksu S, Kufrevioglu OI, Innocenti A, Scozzafava A, Supuran CT: Kinetic and docking studies of phenol-based inhibitors of carbonic anhydrase isoforms I, II, IX and XII evidence a new binding mode within the enzyme active site. Bioorg Med Chem. 2011 Feb 15;19(4):1381-9. doi: 10.1016/j.bmc.2011.01.016. Epub 2011 Jan 14. [21282059 ]
  3. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  4. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA12
Uniprot ID:
O43570
Molecular Weight:
39450.615 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory27.6 uMNot AvailableBindingDB 50009369
References
  1. Carta F, Temperini C, Innocenti A, Scozzafava A, Kaila K, Supuran CT: Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22. doi: 10.1021/jm1003667. [20590092 ]
  2. Durdagi S, Senturk M, Ekinci D, Balaydin HT, Goksu S, Kufrevioglu OI, Innocenti A, Scozzafava A, Supuran CT: Kinetic and docking studies of phenol-based inhibitors of carbonic anhydrase isoforms I, II, IX and XII evidence a new binding mode within the enzyme active site. Bioorg Med Chem. 2011 Feb 15;19(4):1381-9. doi: 10.1016/j.bmc.2011.01.016. Epub 2011 Jan 14. [21282059 ]
  3. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  4. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Zinc ion binding
Specific Function:
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
Gene Name:
CA2
Uniprot ID:
P00918
Molecular Weight:
29245.895 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory84 uMNot AvailableBindingDB 50009369
References
  1. Carta F, Temperini C, Innocenti A, Scozzafava A, Kaila K, Supuran CT: Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22. doi: 10.1021/jm1003667. [20590092 ]
  2. Durdagi S, Senturk M, Ekinci D, Balaydin HT, Goksu S, Kufrevioglu OI, Innocenti A, Scozzafava A, Supuran CT: Kinetic and docking studies of phenol-based inhibitors of carbonic anhydrase isoforms I, II, IX and XII evidence a new binding mode within the enzyme active site. Bioorg Med Chem. 2011 Feb 15;19(4):1381-9. doi: 10.1016/j.bmc.2011.01.016. Epub 2011 Jan 14. [21282059 ]
  3. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  4. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.
Gene Name:
CA9
Uniprot ID:
Q16790
Molecular Weight:
49697.36 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory13.3 uMNot AvailableBindingDB 50009369
References
  1. Carta F, Temperini C, Innocenti A, Scozzafava A, Kaila K, Supuran CT: Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22. doi: 10.1021/jm1003667. [20590092 ]
  2. Durdagi S, Senturk M, Ekinci D, Balaydin HT, Goksu S, Kufrevioglu OI, Innocenti A, Scozzafava A, Supuran CT: Kinetic and docking studies of phenol-based inhibitors of carbonic anhydrase isoforms I, II, IX and XII evidence a new binding mode within the enzyme active site. Bioorg Med Chem. 2011 Feb 15;19(4):1381-9. doi: 10.1016/j.bmc.2011.01.016. Epub 2011 Jan 14. [21282059 ]
  3. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  4. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Receptor signaling protein activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
Gene Name:
ADRB1
Uniprot ID:
P08588
Molecular Weight:
51322.1 Da
References
  1. Meana C, Bordallo J, Bordallo C, Suarez L, Cantabrana B, Sanchez M: Functional effects of polyamines via activation of human beta1- and beta2-adrenoceptors stably expressed in CHO cells. Pharmacol Rep. 2010 Jul-Aug;62(4):696-706. [20885010 ]
  2. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  3. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Protein homodimerization activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.
Gene Name:
ADRB2
Uniprot ID:
P07550
Molecular Weight:
46458.32 Da
References
  1. Meana C, Bordallo J, Bordallo C, Suarez L, Cantabrana B, Sanchez M: Functional effects of polyamines via activation of human beta1- and beta2-adrenoceptors stably expressed in CHO cells. Pharmacol Rep. 2010 Jul-Aug;62(4):696-706. [20885010 ]
  2. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  3. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Metal ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA14
Uniprot ID:
Q9ULX7
Molecular Weight:
37667.37 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.86 uMNot AvailableBindingDB 50009369
References
  1. Carta F, Temperini C, Innocenti A, Scozzafava A, Kaila K, Supuran CT: Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22. doi: 10.1021/jm1003667. [20590092 ]
  2. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  3. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA3
Uniprot ID:
P07451
Molecular Weight:
29557.215 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory167 uMNot AvailableBindingDB 50009369
References
  1. Carta F, Temperini C, Innocenti A, Scozzafava A, Kaila K, Supuran CT: Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22. doi: 10.1021/jm1003667. [20590092 ]
  2. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  3. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
Gene Name:
CA4
Uniprot ID:
P22748
Molecular Weight:
35032.075 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.01 uMNot AvailableBindingDB 50009369
References
  1. Carta F, Temperini C, Innocenti A, Scozzafava A, Kaila K, Supuran CT: Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22. doi: 10.1021/jm1003667. [20590092 ]
  2. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  3. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Low activity.
Gene Name:
CA5A
Uniprot ID:
P35218
Molecular Weight:
34750.21 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.84 uMNot AvailableBindingDB 50009369
References
  1. Carta F, Temperini C, Innocenti A, Scozzafava A, Kaila K, Supuran CT: Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22. doi: 10.1021/jm1003667. [20590092 ]
  2. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  3. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA5B
Uniprot ID:
Q9Y2D0
Molecular Weight:
36433.43 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.83 uMNot AvailableBindingDB 50009369
References
  1. Carta F, Temperini C, Innocenti A, Scozzafava A, Kaila K, Supuran CT: Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22. doi: 10.1021/jm1003667. [20590092 ]
  2. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  3. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Its role in saliva is unknown.
Gene Name:
CA6
Uniprot ID:
P23280
Molecular Weight:
35366.615 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.99 uMNot AvailableBindingDB 50009369
References
  1. Carta F, Temperini C, Innocenti A, Scozzafava A, Kaila K, Supuran CT: Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22. doi: 10.1021/jm1003667. [20590092 ]
  2. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  3. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA7
Uniprot ID:
P43166
Molecular Weight:
29658.235 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.71 uMNot AvailableBindingDB 50009369
References
  1. Carta F, Temperini C, Innocenti A, Scozzafava A, Kaila K, Supuran CT: Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. J Med Chem. 2010 Aug 12;53(15):5511-22. doi: 10.1021/jm1003667. [20590092 ]
  2. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  3. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
Senses changes in the extracellular concentration of calcium ions. The activity of this receptor is mediated by a G-protein that activates a phosphatidylinositol-calcium second messenger system.
Gene Name:
CASR
Uniprot ID:
P41180
Molecular Weight:
120672.385 Da
References
  1. El Hiani Y, Ahidouch A, Roudbaraki M, Guenin S, Brule G, Ouadid-Ahidouch H: Calcium-sensing receptor stimulation induces nonselective cation channel activation in breast cancer cells. J Membr Biol. 2006;211(2):127-37. Epub 2006 Oct 14. [17041782 ]
  2. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  3. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Vitamin d binding
Specific Function:
May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.
Gene Name:
KL
Uniprot ID:
Q9UEF7
Molecular Weight:
116179.815 Da
References
  1. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  2. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Superoxide-generating nadph oxidase activity
Specific Function:
Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity.Isoform 4: Involved in redox signaling in vascular cells. Constitutively and NADPH-dependently generates reactive oxygen species (ROS). Modulates the nuclear activation of ERK1/2 and the ELK1 transcription factor, and is capable of inducing nuclear DNA damage. Displays an increased activity relative to isoform 1.
Gene Name:
NOX4
Uniprot ID:
Q9NPH5
Molecular Weight:
66930.995 Da
References
  1. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  2. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
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  2. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]