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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:23
Primary Accession Number DB00594
Secondary Accession Number
  • APRD00790
  • EXPT00514
Name Amiloride
Drug Type
  • Approved
  • Small Molecule
Description A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)
Synonyms
  1. AMR
  2. Amilorida [INN-Spanish]
  3. Amiloride HCL
  4. Amiloride hydrochloride
  5. Amiloride hydrochloride hydrate
  6. Amiloridum [INN-Latin]
  7. Amyloride
Brand Names
  1. Amipramidin
  2. Amipramizid
  3. Amipramizide
  4. Amiprazidine
  5. Guanamprazin
  6. Guanamprazine
  7. Midamor
Brand Mixtures
  1. Alti-Amiloride HCTZ (Amiloride Hcl + Hydrochlorothiazide)
  2. Ami-Hydro Tab (Amiloride Hcl + Hydrochlorothiazide)
  3. Apo-Amilzide Tab (Amiloride Hcl + Hydrochlorothiazide)
  4. Gen-Amilazide (Amiloride Hcl + Hydrochlorothiazide)
  5. Moduret (Amiloride Hcl + Hydrochlorothiazide)
  6. Novamilor Tab USP (Amiloride Hcl + Hydrochlorothiazide)
  7. Nu-Amilzide 5/50 mg Tab (Amiloride Hcl + Hydrochlorothiazide)
  8. Riva-Amilzide 5/50 mg (Amiloride Hcl + Hydrochlorothiazide)
Chemical IUPAC Name 3,5-diamino-6-chloro-N-(diaminomethylidene)pyrazine-2-carboxamide
Chemical Formula C6H8ClN7O
Chemical Structure Structure
CAS Registry Number 2016-88-8
InChI Identifier InChI=1/C6H8ClN7O/c7-2-4(9)13-3(8)1(12-2)5(15)14-6(10)11/h(H4,8,9,13)(H4,10,11,14,15)/f/h8-11H2
InChI Key XSDQTOBWRPYKKA-DTLMUMOOCW
KEGG Drug Not Available
KEGG Compound C06821 Link Image
PubChem Compound 16231 Link Image
PubChem Substance 9039 Link Image
ChEBI ID Not Available
PharmGKB ID PA448368 Link Image
HET ID AMR Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02249510 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/amilor.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/mod1272.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Amiloride Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Cragoe, Belg, pat. 639,386 (1964 to Merck & Co.), C.A. 62, 14698f (1965)
Average Molecular Weight 229.6270
Monoisotopic Molecular Weight 229.0479
State Solid
Melting Point 240 oC
Experimental Water Solubility Slightly soluble Source: PhysProp
Predicted Water Solubility 1.22e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -0.3 Source: PhysProp
Predicted LogP -0.72 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.27 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 8.7
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID 1F5L Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES N\C(N)=N/C(=O)C1=C(N)N=C(N)C(Cl)=N1
Canonical SMILES NC(N)=NC(=O)C1=C(N)N=C(N)C(Cl)=N1
Drug Category
  • Diuretics
  • Sodium channel blockers
ATC Codes
AHFS Codes
  • 40:28.16
Indication For use as adjunctive treatment with thiazide diuretics or other kaliuretic-diuretic agents in congestive heart failure or hypertension.
Pharmacology Amiloride, an antikaliuretic-diuretic agent, is a pyrazine-carbonyl-guanidine that is unrelated chemically to other known antikaliuretic or diuretic agents. It is an antihypertensive, potassium-sparing diuretic that was first approved for use in 1967 and helps to treat hypertension and congestive heart failure. The drug is often used in conjunction with thiazide or loop diuretics. Due to its potassium-sparing capacities, hyperkalemia (high blood potassium levels) are occasionally observed in patients taking amiloride. The risk is high in concurrent use of ACE inhibitors or spironolactone. Patients are also advised not to use potassium-containing salt replacements.
Mechanism of Action Amiloride works by inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys by binding to the amiloride-sensitive sodium channels. This promotes the loss of sodium and water from the body, but without depleting potassium. Amiloride exerts its potassium sparing effect through the inhibition of sodium reabsorption at the distal convoluted tubule, cortical collecting tubule and collecting duct; this decreases the net negative potential of the tubular lumen and reduces both potassium and hydrogen secretion and their subsequent excretion. Amiloride is not an aldosterone antagonist and its effects are seen even in the absence of aldosterone.
Absorption Readily absorbed following oral administration.
Toxicity No data are available in regard to overdosage in humans. The oral LD50 of amiloride hydrochloride (calculated as the base) is 56 mg/kg in mice and 36 to 85 mg/kg in rats, depending on the strain. The most likely signs and symptoms to be expected with overdosage are dehydration and electrolyte imbalance.
Protein Binding Not Available
Biotransformation Amiloride is not metabolized by the liver but is excreted unchanged by the kidneys.
Half Life Plasma half-life varies from 6 to 9 hours.
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Benazepril Increased risk of hyperkaliemia
Candesartan Increased risk of hyperkaliemia
Captopril Increased risk of hyperkaliemia
Cilazapril Increased risk of hyperkaliemia
Dihydroquinidine barbiturate Decreases the antiarrhythmic effect of quinidine
Enalapril Increased risk of hyperkaliemia
Eplerenone The association presents an ncreased risk of hyperkaliemia
Eprosartan Increased risk of hyperkaliemia
Forasartan Increased risk of hyperkaliemia
Fosinopril Increased risk of hyperkaliemia
Irbesartan Increased risk of hyperkaliemia
Lisinopril Increased risk of hyperkaliemia
Losartan Increased risk of hyperkaliemia
Moexipril Increased risk of hyperkaliemia
Perindopril Increased risk of hyperkaliemia
Polystyrene sulfonate Antagonism of action
Potassium Increased risk of hyperkaliemia
Quinapril Increased risk of hyperkaliemia
Quinidine Decreases the antiarrhythmic effect of quinidine
Quinidine barbiturate Decreases the antiarrhythmic effect of quinidine
Ramipril Increased risk of hyperkaliemia
Saprisartan Increased risk of hyperkaliemia
Spirapril Increased risk of hyperkaliemia
Tasosartan Increased risk of hyperkaliemia
Telmisartan Increased risk of hyperkaliemia
Trandolapril Increased risk of hyperkaliemia
Valsartan Increased risk of hyperkaliemia
Food Interactions
  • Avoid drastic changes in dietary habit.
  • Avoid natural licorice.
  • Avoid salt substitutes containing potassium.
  • Take with food to reduce irritation.
Pathways
Name SMPDB Link KEGG Link
Amiloride Pathway SMP00133 Link Image
General References
  1. Wikipedia Link Image
  2. RxList Link Image
  3. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Amiloride-sensitive sodium channel subunit beta
  2. Amiloride-sensitive sodium channel subunit alpha
  3. Amiloride-sensitive amine oxidase [copper-containing]
  4. Amiloride-sensitive cation channel 2, neuronal
  5. Amiloride-sensitive sodium channel subunit delta
  6. Amiloride-sensitive sodium channel subunit gamma
  7. Amiloride-sensitive cation channel 1, neuronal
  8. Sodium/hydrogen exchanger 1
  9. Urokinase-type plasminogen activator
Drug Target 1 [top]
Target 1 ID 27
Target 1 Name Amiloride-sensitive sodium channel subunit beta
Target 1 Synonyms
  1. Beta ENaC
  2. Beta NaCH
  3. ENaCB
  4. Epithelial Na(+) channel subunit beta
  5. Nonvoltage-gated sodium channel 1 subunit beta
  6. SCNEB
Target 1 Gene Name SCNN1B
Target 1 Protein Sequence >Amiloride-sensitive sodium channel subunit beta 
MHVKKYLLKGLHRLQKGPGYTYKELLVWYCDNTNTHGPKRIICEGPKKKAMWFLLTLLFA
ALVCWQWGIFIRTYLSWEVSVSLSVGFKTMDFPAVTICNASPFKYSKIKHLLKDLDELME
AVLERILAPELSHANATRNLNFSIWNHTPLVLIDERNPHHPMVLDLFGDNHNGLTSSSAS
EKICNAHGCKMAMRLCSLNRTQCTFRNFTSATQALTEWYILQATNIFAQVPQQELVEMSY
PGEQMILACLFGAEPCNYRNFTSIFYPHYGNCYIFNWGMTEKALPSANPGTEFGLKLILD
IGQEDYVPFLASTAGVRLMLHEQRSYPFIRDEGIYAMSGTETSIGVLVDKLQRMGEPYSP
CTVNGSEVPVQNFYSDYNTTYSIQACLRSCFQDHMIRNCNCGHYLYPLPRGEKYCNNRDF
PDWAHCYSDLQMSVAQRETCIGMCKESCNDTQYKMTISMADWPSEASEDWIFHVLSQERD
QSTNITLSRKGIVKLNIYFQEFNYRTIEESAANNIVWLLSNLGGQFGFWMGGSVLCLIEF
GEIIIDFVWITIIKLVALAKSLRQRRAQASYAGPPPTVAELVEAHTNFGFQPDTAPRSPN
TGPYPSEQALPIPGTPPPNYDSLRLQPLDVIESDSEGDAI
Target 1 Number of Residues 650
Target 1 Molecular Weight 72660
Target 1 Theoretical pI 6.26
Target 1 GO Classification
Function
transporter activity
ion transporter activity
ion channel activity
cation channel activity
sodium channel activity
amiloride-sensitive sodium channel activity
Process
physiological process
cellular physiological process
transport
ion transport
cation transport
monovalent inorganic cation transport
sodium ion transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in amiloride-sensitive sodium channel activity
Target 1 Specific Function Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 51-71
  • 533-553
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 1004271 Link Image
Target 1 UniProtKB/Swiss-Prot ID P51168 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name SCNNB_HUMAN Link Image
Target 1 PDB ID 1I5H Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Cell membrane
  • apical cell membrane
  • multi- pass membrane protein. Apical membrane of epithelial cel
Target 1 Gene Sequence >1923 bp 
ATGCACGTGAAGAAGTACCTGCTGAAGGGCCTGCATCGGCTGCAGAAGGGCCCCGGCTAC
ACGTACAAGGAGCTGCTGGTGTGGTACTGCGACAACACCAACACCCACGGCCCCAAGCGC
ATCATCTGTGAGGGGCCCAAGAAGAAAGCCATGTGGTTCCTGCTCACCCTGCTCTTCGCC
GCCCTCGTCTGCTGGCAGTGGGGCATCTTCATCAGGACCTACTTGAGCTGGGAGGTCAGC
GTCTCCCTCTCCGTAGGCTTCAAGACCATGGACTTCCCCGCCGTCACCATCTGCAATGCT
AGCCCCTTCAAGTATTCCAAAATCAAGCATTTGCTGAAGGACCTGGATGAGCTGATGGAA
GCTGTCCTGGAGAGAATCCTGGCTCCTGAGCTAAGCCATGCCAATGCCACCAGGAACCTG
AACTTCTCCATCTGGAACCACACACCCCTGGTCCTTATTGATGAACGGAACCCCCACCAC
CCCATGGTCCTTGATCTCTTTGGAGACAACCACAATGGCTTAACAAGCAGCTCAGCATCA
GAAAAGATCTGTAATGCCCACGGGTGCAAAATGGCCATGAGACTATGTAGCCTCAACAGG
ACCCAGTGTACCTTCCGGAACTTCACCAGTGCTACCCAGGCATTGACAGAGTGGTACATC
CTGCAGGCCACCAACATCTTTGCACAGGTGCCACAGCAGGAGCTAGTAGAGATGAGCTAC
CCCGGCGAGCAGATGATCCTGGCCTGCCTATTCGGAGCTGAGCCCTGCAACTACCGGAAC
TTCACGTCCATCTTCTACCCTCACTATGGCAACTGTTACATCTTCAACTGGGGCATGACA
GAGAAGGCACTTCCTTCGGCCAACCCTGGAACTGAATTCGGCCTGAAGTTGATCCTGGAC
ATAGGCCAGGAAGACTACGTCCCCTTCCTTGCGTCCACGGGCGGGGTCAGGCTGATGCTT
CACGAGCAGAGGTCATACCCCTTCATCAGAGATGAGGGCATCTACGCCATGTCGGGGACA
GAGACGTCCATCGGGGTACTCGTGGATAAGCTTCAGCGCATGGGGGAGCCCTACAGCCCG
TGCACCGTGAATGGTTCTGAGGTCCCCGTCCAAAACTTCTACAGTGACTACAACACGACC
TACTCCATCCAGGCCTGTCTTCGCTCCTGCTTCCAAGACCACATGATCCGTAACTGCAAC
TGTGGCCACTACCTGTACCCACTGCCCCGTGGGGAGAAATACTGCAACAACCGGGACTTC
CCAGACTGGGCCCATTGCTACTCAGATCTACAGATGAGCGTGGCGCAGAGAGAGACCTGC
ATTGGCATGTGCAAGGAGTCCTGCAATGACACCCAGTACAAGATGACCATCTCCATGGCT
GACTGGCCTTCTGAGGCCTCCGAGGACTGGATTTTCCACGTCTTGTCTCAGGAGCGGGAC
CAAAGCACCAATATCACCCTGAGCAGGAAGGGAATTGTCAAGCTCAACATCTACTTCCAA
GAATTTAACTATCGCACCATTGAAGAATCAGCAGCCAATAACATCGTCTGGCTGCTCTCG
AATCTGGGTGGCCAGTTTGGCTTCTGGATGGGGGGCTCTGTGCTGTGCCTCATCGAGTTT
GGGGAGATCATCATCGACTTTGTGTGGATCACCATCATCAAGCTGGTGGCCTTGGCCAAG
AGCCTACGGCAGCGGCGAGCCCAAGCCAGCTACGCTGGCCCACCGCCCACCGTGGCCGAG
CTGGTGGAGGCCCACACCAACTTTGGCTTCCAGCCTGACACGGCCCCCCGCAGCCCCAAC
ACTGGGCCCTACCCCAGTGAGCAGGCCCTGCCCATCCCAGGCACCCCGCCCCCCAACTAT
GACTCCCTGCGTCTGCAGCCGCTGGACGTCATCGAGTCTGACAGTGAGGGTGATGCCATC
TAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID SCNN1B Link Image
Target 1 GenAtlas ID SCNN1B Link Image
Target 1 HGNC ID HGNC:10600 Link Image
Target 1 Chromosome Location 16
Target 1 Locus 16p12.2-p12.1
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Arai K, Zachman K, Shibasaki T, Chrousos GP: Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential? J Clin Endocrinol Metab. 1999 Jul;84(7):2434-7. [PubMed Link Image]
  2. Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD: Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q. Genomics. 1999 Sep 15;60(3):295-308. [PubMed Link Image]
  3. McDonald FJ, Western AH, McNeil JD, Thomas BC, Olson DR, Snyder PM: Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel. Am J Physiol Renal Physiol. 2002 Sep;283(3):F431-6. [PubMed Link Image]
  4. Voilley N, Bassilana F, Mignon C, Merscher S, Mattei MG, Carle GF, Lazdunski M, Barbry P: Cloning, chromosomal localization, and physical linkage of the beta and gamma subunits (SCNN1B and SCNN1G) of the human epithelial amiloride-sensitive sodium channel. Genomics. 1995 Aug 10;28(3):560-5. [PubMed Link Image]
  5. Hansson JH, Nelson-Williams C, Suzuki H, Schild L, Shimkets R, Lu Y, Canessa C, Iwasaki T, Rossier B, Lifton RP: Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. Nat Genet. 1995 Sep;11(1):76-82. [PubMed Link Image]
  6. McDonald FJ, Price MP, Snyder PM, Welsh MJ: Cloning and expression of the beta- and gamma-subunits of the human epithelial sodium channel. Am J Physiol. 1995 May;268(5 Pt 1):C1157-63. [PubMed Link Image]
  7. Shimkets RA, Warnock DG, Bositis CM, Nelson-Williams C, Hansson JH, Schambelan M, Gill JR Jr, Ulick S, Milora RV, Findling JW, et al.: Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. 1994 Nov 4;79(3):407-14. [PubMed Link Image]
  8. Hansson JH, Schild L, Lu Y, Wilson TA, Gautschi I, Shimkets R, Nelson-Williams C, Rossier BC, Lifton RP: A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11495-9. [PubMed Link Image]
  9. Chang SS, Grunder S, Hanukoglu A, Rosler A, Mathew PM, Hanukoglu I, Schild L, Lu Y, Shimkets RA, Nelson-Williams C, Rossier BC, Lifton RP: Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet. 1996 Mar;12(3):248-53. [PubMed Link Image]
  10. Pirozzi G, McConnell SJ, Uveges AJ, Carter JM, Sparks AB, Kay BK, Fowlkes DM: Identification of novel human WW domain-containing proteins by cloning of ligand targets. J Biol Chem. 1997 Jun 6;272(23):14611-6. [PubMed Link Image]
  11. 9674649 Persu A, Barbry P, Bassilana F, Houot AM, Mengual R, Lazdunski M, Corvol P, Jeunemaitre X: Genetic analysis of the beta subunit of the epithelial Na+ channel in essential hypertension. Hypertension. 1998 Jul;32(1):129-37.
  12. 9794716 Uehara Y, Sasaguri M, Kinoshita A, Tsuji E, Kiyose H, Taniguchi H, Noda K, Ideishi M, Inoue J, Tomita K, Arakawa K: Genetic analysis of the epithelial sodium channel in Liddle's syndrome. J Hypertens. 1998 Aug;16(8):1131-5.
  13. 9813171 Saxena A, Hanukoglu I, Strautnieks SS, Thompson RJ, Gardiner RM, Hanukoglu A: Gene structure of the human amiloride-sensitive epithelial sodium channel beta subunit. Biochem Biophys Res Commun. 1998 Nov 9;252(1):208-13.
Target 1 Drug References
  1. Brooks HL, Allred AJ, Beutler KT, Coffman TM, Knepper MA: Targeted proteomic profiling of renal Na(+) transporter and channel abundances in angiotensin II type 1a receptor knockout mice. Hypertension. 2002 Feb;39(2 Pt 2):470-3. [PubMed Link Image]
  2. Yamagata T, Yamagata Y, Nishimoto T, Nakanishi M, Nakanishi H, Minakata Y, Mune M, Yukawa S: The impact of phorbol ester on the regulation of amiloride-sensitive epithelial sodium channel in alveolar type ii epithelial cells. Exp Lung Res. 2002 Oct-Nov;28(7):543-62. [PubMed Link Image]
  3. Lebowitz J, An B, Edinger RS, Zeidel ML, Johnson JP: Effect of altered Na+ entry on expression of apical and basolateral transport proteins in A6 epithelia. Am J Physiol Renal Physiol. 2003 Sep;285(3):F524-31. Epub 2003 May 13. [PubMed Link Image]
  4. Kamide K, Tanaka C, Takiuchi S, Miwa Y, Yoshii M, Horio T, Kawano Y, Miyata T: Six missense mutations of the epithelial sodium channel beta and gamma subunits in Japanese hypertensives. Hypertens Res. 2004 May;27(5):333-8. [PubMed Link Image]
  5. Planes C, Leyvraz C, Uchida T, Angelova MA, Vuagniaux G, Hummler E, Matthay M, Clerici C, Rossier B: In vitro and in vivo regulation of transepithelial lung alveolar sodium transport by serine proteases. Am J Physiol Lung Cell Mol Physiol. 2005 Jun;288(6):L1099-109. Epub 2005 Jan 28. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 213
Target 2 Name Amiloride-sensitive sodium channel subunit alpha
Target 2 Synonyms
  1. Alpha ENaC
  2. Alpha NaCH
  3. Epithelial Na(+) channel subunit alpha
  4. Nonvoltage-gated sodium channel 1 subunit alpha
  5. SCNEA
Target 2 Gene Name SCNN1A
Target 2 Protein Sequence >Amiloride-sensitive sodium channel subunit alpha 
MEGNKLEEQDSSPPQSTPGLMKGNKREEQGLGPEPAAPQQPTAEEEALIEFHRSYRELFE
FFCNNTTIHGAIRLVCSQHNRMKTAFWAVLWLCTFGMMYWQFGLLFGEYFSYPVSLNINL
NSDKLVFPAVTICTLNPYRYPEIKEELEELDRITEQTLFDLYKYSSFTTLVAGSRSRRDL
RGTLPHPLQRLRVPPPPHGARRARSVASSLRDNNPQVDWKDWKIGFQLCNQNKSDCFYQT
YSSGVDAVREWYRFHYINILSRLPETLPSLEEDTLGNFIFACRFNQVSCNQANYSHFHHP
MYGNCYTFNDKNNSNLWMSSMPGINNGLSLMLRAEQNDFIPLLSTVTGARVMVHGQDEPA
FMDDGGFNLRPGVETSISMRKETLDRLGGDYGDCTKNGSDVPVENLYPSKYTQQVCIHSC
FQESMIKECGCAYIFYPRPQNVEYCDYRKHSSWGYCYYKLQVDFSSDHLGCFTKCRKPCS
VTSYQLSAGYSRWPSVTSQEWVFQMLSRQNNYTVNNKRNGVAKVNIFFKELNYKTNSESP
SVTMVTLLSNLGSQWSLWFGSSVLSVVEMAELVFDLLVIMFLMLLRRFRSRYWSPGRGGR
GAQEVASTLASSPPSHFCPHPMSLSLSQPGPAPSPALTAPPPAYATLGPRPSPGGSAGAS
SSTCPLGGP
Target 2 Number of Residues 680
Target 2 Molecular Weight 75704
Target 2 Theoretical pI 7.54
Target 2 GO Classification
Function
transporter activity
ion transporter activity
ion channel activity
cation channel activity
sodium channel activity
amiloride-sensitive sodium channel activity
Process
physiological process
cellular physiological process
transport
ion transport
cation transport
monovalent inorganic cation transport
sodium ion transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in amiloride-sensitive sodium channel activity
Target 2 Specific Function Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 86-106
  • 563-583
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 452650 Link Image
Target 2 UniProtKB/Swiss-Prot ID P37088 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name SCNNA_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Cell membrane
  • apical cell membrane
  • multi- pass membrane protein. Apical membrane of epithelial cel
Target 2 Gene Sequence >2010 bp 
ATGGAGGGGAACAAGCTGGAGGAGCAGGACTCTAGCCCTCCACAGTCCACTCCAGGGCTC
ATGAAGGGGAACAAGCGTGAGGAGCAGGGGCTGGGCCCCGAACCTGCGGCGCCCCAGCAG
CCCACGGCGGAGGAGGAGGCCCTGATCGAGTTCCACCGCTCCTACCGAGAGCTCTTCGAG
TTCTTCTGCAACAACACCACCATCCACGGCGCCATCCGCCTGGTGTGCTCCCAGCACAAC
CGCATGAAGACGGCCTTCTGGGCAGTGCTGTGGCTCTGCACCTTTGGCATGATGTACTGG
CAATTCGGCCTGCTTTTCGGAGAGTACTTCAGCTACCCCGTCAGCCTCAACATCAACCTC
AACTCGGACAAGCTCGTCTTCCCCGCAGTGACCATCTGCACCCTCAATCCCTACAGGTAC
CCGGAAATTAAAGAGGAGCTGGAGGAGCTGGACCGCATCACAGAGCAGACGCTCTTTGAC
CTGTACAAATACAGCTCCTTCACCACTCTCGTGGCCGGCTCCCGCAGCCGTCGCGACCTG
CGGGGGACTCTGCCGCACCCCTTGCAGCGCCTGAGGGTCCCGCCCCCGCCTCACGGGGCC
CGTCGAGCCCGTAGCGTGGCCTCCAGCTTGCGGGACAACAACCCCCAGGTGGACTGGAAG
GACTGGAAGATCGGCTTCCAGCTGTGCAACCAGAACAAATCGGACTGCTTCTACCAGACA
TACTCATCAGGGGTGGATGCGGTGAGGGAGTGGTACCGCTTCCACTACATCAACATCCTG
TCGAGGCTGCCAGAGACTCTGCCATCCCTGGAGGAGGACACGCTGGGCAACTTCATCTTC
GCCTGCCGCTTCAACCAGGTCTCCTGCAACCAGGCGAATTACTCTCACTTCCACCACCCG
ATGTATGGAAACTGCTATACTTTCAATGACAAGAACAACTCCAACCTCTGGATGTCTTCC
ATGCCTGGAATCAACAACGGTCTGTCCCTGATGCTGCGCGCAGAGCAGAATGACTTCATT
CCCCTGCTGTCCACAGTGACTGGGGCCCGGGTAATGGTGCACGGGCAGGATGAACCTGCC
TTTATGGATGATGGTGGCTTTAACTTGCGGCCTGGCGTGGAGACCTCCATCAGCATGAGG
AAGGAAACCCTGGACAGACTTGGGGGCGATTATGGCGACTGCACCAAGAATGGCAGTGAT
GTTCCTGTTGAGAACCTTTACCCTTCAAAGTACACACAGCAGGTGTGTATTCACTCCTGC
TTCCAGGAGAGCATGATCAAGGAGTGTGGCTGTGCCTACATCTTCTATCCGCGGCCCCAG
AACGTGGAGTACTGTGACTACAGAAAGCACAGTTCCTGGGGGTACTGCTACTATAAGCTC
CAGGTTGACTTCTCCTCAGACCACCTGGGCTGTTTCACCAAGTGCCGGAAGCCATGCAGC
GTGACCAGCTACCAGCTCTCTGCTGGTTACTCACGATGGCCCTCGGTGACATCCCAGGAA
TGGGTCTTCCAGATGCTATCGCGACAGAACAATTACACCGTCAACAACAAGAGAAATGGA
GTGGCCAAAGTCAACATCTTCTTCAAGGAGCTGAACTACAAAACCAATTCTGAGTCTCCC
TCTGTCACGATGGTCACCCTCCTGTCCAACCTGGGCAGCCAGTGGAGCCTGTGGTTCGGC
TCCTCGGTGTTGTCTGTGGTGGAGATGGCTGAGCTCGTCTTTGACCTGCTGGTCATCATG
TTCCTCATGCTGCTCCGAAGGTTCCGAAGCCGATACTGGTCTCCAGGCCGAGGGGGCAGG
GGTGCTCAGGAGGTAGCCTCCACCCTGGCATCCTCCCCTCCTTCCCACTTCTGCCCCCAC
CCCATGTCTCTGTCCTTGTCCCAGCCAGGCCCTGCTCCCTCTCCAGCCTTGACAGCCCCT
CCCCCTGCCTATGCCACCCTGGGCCCCCGCCCATCTCCAGGGGGCTCTGCAGGGGCCAGT
TCCTCCACCTGTCCTCTGGGGGGGCCCTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID SCNN1A Link Image
Target 2 GenAtlas ID SCNN1A Link Image
Target 2 HGNC ID HGNC:10599 Link Image
Target 2 Chromosome Location 12
Target 2 Locus 12p13
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Arai K, Zachman K, Shibasaki T, Chrousos GP: Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential? J Clin Endocrinol Metab. 1999 Jul;84(7):2434-7. [PubMed Link Image]
  2. Chow YH, Wang Y, Plumb J, O'Brodovich H, Hu J: Hormonal regulation and genomic organization of the human amiloride-sensitive epithelial sodium channel alpha subunit gene. Pediatr Res. 1999 Aug;46(2):208-14. [PubMed Link Image]
  3. Schaedel C, Marthinsen L, Kristoffersson AC, Kornfalt R, Nilsson KO, Orlenius B, Holmberg L: Lung symptoms in pseudohypoaldosteronism type 1 are associated with deficiency of the alpha-subunit of the epithelial sodium channel. J Pediatr. 1999 Dec;135(6):739-45. [PubMed Link Image]
  4. Mick VE, Itani OA, Loftus RW, Husted RF, Schmidt TJ, Thomas CP: The alpha-subunit of the epithelial sodium channel is an aldosterone-induced transcript in mammalian collecting ducts, and this transcriptional response is mediated via distinct cis-elements in the 5'-flanking region of the gene. Mol Endocrinol. 2001 Apr;15(4):575-88. [PubMed Link Image]
  5. McDonald FJ, Western AH, McNeil JD, Thomas BC, Olson DR, Snyder PM: Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel. Am J Physiol Renal Physiol. 2002 Sep;283(3):F431-6. [PubMed Link Image]
  6. McDonald FJ, Snyder PM, McCray PB Jr, Welsh MJ: Cloning, expression, and tissue distribution of a human amiloride-sensitive Na+ channel. Am J Physiol. 1994 Jun;266(6 Pt 1):L728-34. [PubMed Link Image]
  7. Voilley N, Lingueglia E, Champigny G, Mattei MG, Waldmann R, Lazdunski M, Barbry P: The lung amiloride-sensitive Na+ channel: biophysical properties, pharmacology, ontogenesis, and molecular cloning. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):247-51. [PubMed Link Image]
  8. Pirozzi G, McConnell SJ, Uveges AJ, Carter JM, Sparks AB, Kay BK, Fowlkes DM: Identification of novel human WW domain-containing proteins by cloning of ligand targets. J Biol Chem. 1997 Jun 6;272(23):14611-6. [PubMed Link Image]
  9. Tucker JK, Tamba K, Lee YJ, Shen LL, Warnock DG, Oh Y: Cloning and functional studies of splice variants of the alpha-subunit of the amiloride-sensitive Na+ channel. Am J Physiol. 1998 Apr;274(4 Pt 1):C1081-9. [PubMed Link Image]
  10. Thomas CP, Auerbach S, Stokes JB, Volk KA: 5' heterogeneity in epithelial sodium channel alpha-subunit mRNA leads to distinct NH2-terminal variant proteins. Am J Physiol. 1998 May;274(5 Pt 1):C1312-23. [PubMed Link Image]
  11. 9654208 Ludwig M, Bolkenius U, Wickert L, Marynen P, Bidlingmaier F: Structural organisation of the gene encoding the alpha-subunit of the human amiloride-sensitive epithelial sodium channel. Hum Genet. 1998 May;102(5):576-81.
Target 2 Drug References
  1. Kelly O, Lin C, Ramkumar M, Saxena NC, Kleyman TR, Eaton DC: Characterization of an amiloride binding region in the alpha-subunit of ENaC. Am J Physiol Renal Physiol. 2003 Dec;285(6):F1279-90. Epub 2003 Aug 19. [PubMed Link Image]
  2. Ji HL, Benos DJ: Degenerin sites mediate proton activation of deltabetagamma-epithelial sodium channel. J Biol Chem. 2004 Jun 25;279(26):26939-47. Epub 2004 Apr 14. [PubMed Link Image]
  3. Otulakowski G, Duan W, Gandhi S, O'brodovich H: Steroid and Oxygen Effects on eIF4F Complex, mTOR, and ENaC Translation in Fetal Lung Epithelia. Am J Respir Cell Mol Biol. 2007 Oct;37(4):457-466. Epub 2007 Jun 7. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 387
Target 3 Name Amiloride-sensitive amine oxidase [copper-containing]
Target 3 Synonyms
  1. ABP
  2. Amiloride-binding protein
  3. Amiloride-sensitive amine oxidase precursor
  4. DAO
  5. Diamine oxidase
  6. EC 1.4.3.6
  7. Histaminase
  8. KAO
  9. Kidney amine oxidase
Target 3 Gene Name ABP1
Target 3 Protein Sequence >Amiloride-sensitive amine oxidase [copper-containing] precursor 
MPALGWAVAAILMLQTAMAEPSPGTLPRKAGVFSDLSNQELKAVHSFLWSKKELRLQPSS
TTTMAKNTVFLIEMLLPKKYHVLRFLDKGERHPVREARAVIFFGDQEHPNVTEFAVGPLP
GPCYMRALSPRPGYQSSWASRPISTAEYALLYHTLQEATKPLHQFFLNTTGFSFQDCHDR
CLAFTDVAPRGVASGQRRSWLIIQRYVEGYFLHPTGLELLVDHGSTDAGHWAVEQVWYNG
KFYGSPEELARKYADGEVDVVVLEDPLPGGKGHDSTEEPPLFSSHKPRGDFPSPIHVSGP
RLVQPHGPRFRLEGNAVLYGGWSFAFRLRSSSGLQVLNVHFGGERIAYEVSVQEAVALYG
GHTPAGMQTKYLDVGWGLGSVTHELAPGIDCPETATFLDTFHYYDADDPVHYPRALCLFE
MPTGVPLRRHFNSNFKGGFNFYAGLKGQVLVLRTTSTVYNYDYIWDFIFYPNGVMEAKMH
ATGYVHATFYTPEGLRHGTRLHTHLIGNIHTHLVHYRVDLDVAGTKNSFQTLQMKLENIT
NPWSPRHRVVQPTLEQTQYSWERQAAFRFKRKLPKYLLFTSPQENPWGHKRSYRLQIHSM
ADQVLPPGWQEEQAITWARYPLAVTKYRESELCSSSIYHQNDPWDPPVVFEQFLHNNENI
ENEDLVAWVTVGFLHIPHSEDIPNTATPGNSVGFLLRPFNFFPEDPSLASRDTVIVWPRD
NGPNYVQRWIPEDRDCSMPPPFSYNGTYRPV
Target 3 Number of Residues 763
Target 3 Molecular Weight 85342
Target 3 Theoretical pI 7.01
Target 3 GO Classification
Function
binding
ion binding
cation binding
transition metal ion binding
copper ion binding
Process
Not Available
Component
Not Available
Target 3 General Function Secondary metabolites biosynthesis, transport and catabolism
Target 3 Specific Function Catalyzes the degradation of compounds such as putrescine, histamine, spermine, and spermidine, substances involved in allergic and immune responses, cell proliferation, tissue differentiation, tumor formation, and possibly apoptosis. Placental DAO is thought to play a role in the regulation of the female reproductive function
Target 3 Pathways
Name SMPDB Link KEGG Link
Alkaloid biosynthesis II map00960 Link Image
Arginine and proline metabolism SMP00020 Link Image map00330 Link Image
Glycine, serine and threonine metabolism SMP00004 Link Image map00260 Link Image
Histidine metabolism SMP00044 Link Image map00340 Link Image
Phenylalanine metabolism map00360 Link Image
Tryptophan metabolism SMP00063 Link Image map00380 Link Image
Tyrosine metabolism SMP00006 Link Image map00350 Link Image
beta-Alanine metabolism SMP00007 Link Image map00410 Link Image
Target 3 Reactions
  • RCH2NH2 + H2O + O2 = RCHO + NH3 + H2O2
Target 3 Pfam Domain Function
Target 3 Signals
  • 1-19
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 177960 Link Image
Target 3 UniProtKB/Swiss-Prot ID P19801 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name ABP1_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Secreted protein
  • extracellular space
Target 3 Gene Sequence >2256 bp 
ATGCCGGCCCTGGGCTGGGCCGTGGCTGCCATCCTGATGCTGCAGACGGCCATGGCGGAG
CCCTCCCCGGGGACTCTGCCCAGGAAGGCAGGGGTGTTTTCAGACCTAAGCAACCAAGAG
CTGAAGGCAGTGCACAGCTTCCTCTGGTCCAAGAAGGAGCTGAGGCTGCAGCCCTCCAGT
ACCACCACCATGGCCAAGAACACCGTGTTTCTCATCGAGATGCTGCTGCCCAAGAAGTAC
CATGTGCTGAGGTTTCTGGATAAAGGTGAAAGGCATCCTGTGCGGGAAGCCCGTGCCGTC
ATCTTCTTTGGTGACCAGGAGCATCCCAATGTCACCGAGTTTGCTGTGGGGCCCCTGCCA
GGGCCCTGCTACATGCGAGCACTGTCCCCCAGGCCTGGGTACCAGTCCTCCTGGGCATCG
AGGCCCATCTCCACAGCAGAGTATGCCCTCCTCTACCACACCCTGCAGGAAGCCACCAAG
CCCCTGCATCAGTTCTTCCTCAATACCACAGGCTTCTCATTCCAAGACTGCCATGACAGA
TGCCTGGCCTTCACCGATGTGGCCCCCCGGGGTGTGGCTTCTGGCCAGCGCCGCAGTTGG
CTTATCATACAGCGCTATGTAGAAGGCTACTTTCTGCACCCCACTGGGCTGGAGCTCCTC
GTGGATCATGGGAGCACAGATGCTGGGCACTGGGCCGTGGAGCAGGTGTGGTACAACGGG
AAGTTCTATGGGAGCCCAGAGGAACTGGCTCGGAAGTATGCAGATGGAGAGGTGGACGTG
GTGGTCCTGGAGGACCCGCTGCCTGGGGGCAAGGGGCATGACAGCACAGAGGAGCCGCCC
CTCTTCTCCTCCCACAAGCCCCGCGGGGACTTCCCCAGCCCCATCCATGTGAGCGGCCCC
CGCTTGGTCCAGCCCCACGGCCCTCGCTTCAGGCTGGAGGGCAACGCTGTGCTCTACGGC
GGCTGGAGCTTTGCCTTCCGGCTGCGCTCCTCCTCCGGGCTGCAGGTCCTGAACGTGCAC
TTCGGCGGAGAGCGCATTGCCTATGAGGTCAGCGTGCAAGAGGCAGTGGCGCTGTATGGA
GGACACACACCTGCAGGCATGCAGACCAAGTACCTCGATGTCGGCTGGGGCCTGGGCAGC
GTCACTCATGAGTTAGCCCCCGGCATCGACTGCCCGGAGACCGCCACCTTCCTGGACACT
TTCCACTACTATGATGCCGATGACCCGGTCCATTATCCCCGAGCCCTCTGCCTCTTTGAA
ATGCCCACAGGGGTGCCCCTTCGGCGGCACTTTAATTCCAACTTTAAAGGTGGCTTCAAC
TTCTATGCGGGGCTGAAGGGCCAGGTGCTGGTGCTGCGGACAACTTCAACTGTCTACAAT
TATGATTACATTTGGGACTTTATCTTCTACCCCAACGGGGTGATGGAGGCCAAGATGCAT
GCCACTGGCTACGTCCACGCCACCTTCTACACCCCCGAGGGGCTGCGCCACGGCACTCGC
CTGCACACCCACCTGATTGGCAACATACACACTCACTTGGTGCACTACCGCGTAGACCTG
GATGTGGCAGGCACCAAGAACAGCTTCCAGACACTGCAGATGAAGCTAGAAAACATCACC
AACCCCTGGAGCCCAAGACACCGCGTGGTCCAGCCAACTCTGGAGCAGACGCAGTACTCC
TGGGAGCGCCAGGCGGCCTTCCGCTTCAAAAGGAAGCTGCCCAAGTACCTGCTCTTTACC
AGCCCCCAGGAGAACCCCTGGGGCCACAAGCGCAGCTACCGCCTGCAGATCCACTCCATG
GCCGACCAGGTGCTGCCCCCAGGCTGGCAGGAGGAGCAGGCCATCACCTGGGCAAGGTAC
CCCCTGGCAGTGACCAAGTACCGGGAGTCGGAGCTGTGCAGCAGCAGCATCTACCACCAG
AACGACCCCTGGCACCCGCCCGTGGTCTTTGAGCAGTTTCTTCACAACAACGAGAACATT
GAAAATGAGGACCTGGTGGCCTGGGTGACGGTGGGCTTCCTGCACATCCCCCACTCAGAG
GACATTCCCAACACAGCCACACCTGGGAACTCCGTGGGCTTCCTGCTCCGGCCATTCAAC
TTCTTCCCAGAGGACCCCTCCCTGGCATCCAGAGACACTGTGATCGTGTGGCCTCGGGAC
AACGGCCCCAACTACGTCCAGCGCTGGATCCCTGAGGACAGGGACTGCTCGATGCCTCCC
CCTTTTAGCTACAATGGGACCTATAGACCTGTGTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID ABP1 Link Image
Target 3 GenAtlas ID ABP1 Link Image
Target 3 HGNC ID HGNC:80 Link Image
Target 3 Chromosome Location 7
Target 3 Locus 7q34-q36
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Barbry P, Champe M, Chassande O, Munemitsu S, Champigny G, Lingueglia E, Maes P, Frelin C, Tartar A, Ullrich A, et al.: Human kidney amiloride-binding protein: cDNA structure and functional expression. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7347-51. [PubMed Link Image]
  2. Novotny WF, Chassande O, Baker M, Lazdunski M, Barbry P: Diamine oxidase is the amiloride-binding protein and is inhibited by amiloride analogues. J Biol Chem. 1994 Apr 1;269(13):9921-5. [PubMed Link Image]
  3. Chassande O, Renard S, Barbry P, Lazdunski M: The human gene for diamine oxidase, an amiloride binding protein. Molecular cloning, sequencing, and characterization of the promoter. J Biol Chem. 1994 May 20;269(20):14484-9. [PubMed Link Image]
  4. Zhang X, Kim J, McIntire WS: cDNA sequences of variant forms of human placenta diamine oxidase. Biochem Genet. 1995 Aug;33(7-8):261-8. [PubMed Link Image]
Target 3 Drug References
  1. Padiglia A, Medda R, Lorrai A, Murgia B, Pedersen JZ, Agro AF, Floris G: Interaction of pig kidney and lentil seedling copper-containing amine oxidases with guanidinium compounds. J Enzyme Inhib. 2000;15(1):91-100. [PubMed Link Image]
  2. Padiglia A, Medda R, Lorrai A, Murgia B, Pedersen JZ, Finazzi Agro A, Floris G: Interaction of Pig Kidney and Lentil Seedling Copper-Containing Amine Oxidases with Guanidinium Compounds. J Enzyme Inhib. 1999 Nov;15(1):91-100. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 389
Target 4 Name Amiloride-sensitive cation channel 2, neuronal
Target 4 Synonyms
  1. ASIC1
  2. Acid-sensing ion channel 1
  3. BNaC2
  4. Brain sodium channel 2
Target 4 Gene Name ACCN2
Target 4 Protein Sequence >Amiloride-sensitive cation channel 2, neuronal 
MELKAEEEEVGGVQPVSIQAFASSSTLHGLAHIFSYERLSLKRALWALCFLGSLAVLLCV
CTERVQYYFHYHHVTKLDEVAASQLTFPAVTLCNLNEFRFSQVSKNDLYHAGELLALLNN
RYEIPDTQMADEKQLEILQDKANFRSFKPKPFNMREFYDRAGHDIRDMLLSCHFRGEVCS
AEDFKVVFTRYGKCYTFNSGRDGRPRLKTMKDGTGNGLEIMLDIQQDEYLPVWGETDETS
FEAGIKVQIHSQDEPPFIDQLGFGVAPGFQTFVACQEQRLIYLPPPWGTCKAVTMDSDLD
FFDSYSITACRIDCETRYLVENCNCRMVHMPGDAPYCTPEQYKECADPALDFLVEKDQEY
CVCEMPCNLTRYGKELSMVKIPSKASAKYLAKKFNKSEQYIGENILVLDIFFEVLNYETI
EQKKAYEIAGLLGDIGGQMGLFIGASILTVLELFDYAYEVIKHKLCRRGKCQKEAKRSSA
DKGVALSLDDVKRHNPCESLRGHPAGMTYAANILPHHPARGTFEDFTC
Target 4 Number of Residues 536
Target 4 Molecular Weight 59968
Target 4 Theoretical pI 5.39
Target 4 GO Classification
Function
transporter activity
ion transporter activity
ion channel activity
cation channel activity
sodium channel activity
amiloride-sensitive sodium channel activity
Process
physiological process
cellular physiological process
transport
ion transport
cation transport
monovalent inorganic cation transport
sodium ion transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 4 General Function Involved in amiloride-sensitive sodium channel activity
Target 4 Specific Function Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Ca(2+), Li(+) and K(+). Generates a biphasic current with a fast inactivating and a slow sustained phase. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • 45-65
  • 428-448
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 1871168 Link Image
Target 4 UniProtKB/Swiss-Prot ID P78348 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name ACCN2_HUMAN Link Image
Target 4 PDB ID Not Available
Target 4 Cellular Location
  • Cell membrane
  • multi-pass membrane protein. Localizes in synaptosomes at dendritic synapses of neuro
Target 4 Gene Sequence >1587 bp 
ATGGAACTGAAGGCCGAGGAGGAGGAGGTGGGTGGCGTCCAGCCGGTGAGCATCCAGGCC
TTCGCCAGCAGCTCCACACTGCACGGCCTGGCCCACATCTTCTCCTACGAGCGGCTGTCT
CTGAAGCGGGCACTGTGGGCCCTGTGCTTCCTGGGCTCGCTGGCTGTGCTGCTGTGTGTG
TGCACGGAGCGTGTGCAGTACTACTTCCACTACCACCATGTCACCAAGCTCGACGAGGTG
GCTGCCTCTCAGCTTACCTTCCCTGCTGTCACGCTGTGCAACCTCAACGAGTTCCGCTTT
AGCCAAGTCTCCAAGAATGACCTGTATCATGCTGGGGAGCTGCTGGCCCTGCTCAACAAC
AGGTATGAGATACCAGACACACAGATGGCAGATGAAAAGCAGCTGGAGATACTGCAGGAC
AAAGCCAACTTCCGCAGCTTCAAACCCAAACCCTTCAACATGCGTGAGTTCTACGACCGA
GCTGGGCACGACATTCGAGACATGCTGCTCTCCTGCCACTTCCGGGGGGAGGTCTGCAGC
GCTGAAGACTTCAAGGTGGTCTTCACACGCTATGGAAAGTGCTACACGTTCAACTCGGGC
CGAGATGGGCGGCCGCGGCTGAAGACCATGAAGGATGGGACGGGCAATGGGCTGGAAATC
ATGCTGGACATCCAGCAGGACGAGTACCTGCCTGTGTGGGGGGAGACTGACGAGACGTCC
TTCGAAGCAGGCATCAAAGTGCAGATCCATAGTCAGGATGAACCTCCTTTCATCGACCAG
CTGGGCTTTGGCGTGGCCCCAGGCTTCCAGACCTTTGTGGCCTGCCAGGAGCAGCGGCTC
ATCTACCTGCCCCCACCCTGGGGCACCTGCAAAGCTGTTACCATGGACTCGGATTTGGAT
TTCTTCGACTCCTACAGCATCACTGCCTGCCGCATCGACTGTGAGACGCGCTACCTGGTG
GAGAACTGCAACTGCCGCATGGTGCACATGCCAGGGGATGCCCCATACTGTACTCCAGAG
CAGTACAAGGAGTGTGCAGATCCTGCTCTGGACTTCCTGGTGGAGAAGGACCAGGAGTAC
TGCGTGTGTGAAATGCCTTGCAACCTGACCCGCTATGGCAAAGAGCTGTCCATGGTCAAG
ATCCCCAGCAAAGCCTCAGCCAAGTACCTGGCCAAGAAGTTCAACAAATCTGAGCAATAC
ATAGGGGAGAACATCCTGGTGCTGGACATTTTCTTTGAAGTCCTCAACTATGAGACCATT
GAACAGAAGAAGGCCTATGAGATTGCAGGGCTCCTGGGTGACATCGGGGGCCAGATGGGG
CTGTTCATCGGGGCCAGCATCCTCACGGTGCTGGAGCTCTTTGACTACGCCTACGAGGTC
ATTAAGCACAAGCTGTGCCGACGAGGAAAATGCCAGAAGGAGGCCAAAAGGAGCAGTGCG
GACAAGGGCGTGGCCCTCAGCCTGGACGACGTCAAAAGACACAACCCGTGCGAGAGCCTT
CGGGGCCACCCTGCCGGGATGACATACGCTGCCAACATCCTACCTCACCATCCGGCCCGA
GGCACGTTCGAGGACTTTACCTGCTGA
Target 4 GenBank Gene ID
Target 4 GeneCard ID ACCN2 Link Image
Target 4 GenAtlas ID ACCN2 Link Image
Target 4 HGNC ID HGNC:100 Link Image
Target 4 Chromosome Location 12
Target 4 Locus 12q12
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Hruska-Hageman AM, Wemmie JA, Price MP, Welsh MJ: Interaction of the synaptic protein PICK1 (protein interacting with C kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel). Biochem J. 2002 Feb 1;361(Pt 3):443-50. [PubMed Link Image]
  2. Garcia-Anoveros J, Derfler B, Neville-Golden J, Hyman BT, Corey DP: BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1459-64. [PubMed Link Image]
Target 4 Drug References
  1. Petruska JC, Napaporn J, Johnson RD, Cooper BY: Chemical responsiveness and histochemical phenotype of electrophysiologically classified cells of the adult rat dorsal root ganglion. Neuroscience. 2002;115(1):15-30. [PubMed Link Image]
  2. Jones NG, Slater R, Cadiou H, McNaughton P, McMahon SB: Acid-induced pain and its modulation in humans. J Neurosci. 2004 Dec 1;24(48):10974-9. [PubMed Link Image]
  3. Sugiura T, Dang K, Lamb K, Bielefeldt K, Gebhart GF: Acid-sensing properties in rat gastric sensory neurons from normal and ulcerated stomach. J Neurosci. 2005 Mar 9;25(10):2617-27. [PubMed Link Image]
  4. Wang W, Duan B, Xu H, Xu L, Xu TL: Calcium-permeable acid-sensing ion channel is a molecular target of the neurotoxic metal ion lead. J Biol Chem. 2006 Feb 3;281(5):2497-505. Epub 2005 Nov 29. [PubMed Link Image]
  5. Xiong ZG, Chu XP, Simon RP: Ca2+ -permeable acid-sensing ion channels and ischemic brain injury. J Membr Biol. 2006 Jan;209(1):59-68. Epub 2006 Apr 17. [PubMed Link Image]
Drug Target 5 [top]
Target 5 ID 550
Target 5 Name Amiloride-sensitive sodium channel subunit delta
Target 5 Synonyms
  1. Delta ENaC
  2. Delta NaCH
  3. Epithelial Na(+) channel subunit delta
  4. Nonvoltage-gated sodium channel 1 subunit delta
  5. SCNED
Target 5 Gene Name SCNN1D
Target 5 Protein Sequence >Amiloride-sensitive sodium channel subunit delta 
MAEHRSMDGRMEAATRGGSHLQAAAQTPPRPGPPSAPPPPPKEGHQEGLVELPASFRELL
TFFCTNATIHGAIRLVCSRGNRLKTTSWGLLSLGALVALCWQLGLLFERHWHRPVLMAVS
VHSERKLLPLVTLCDGNPRRPSPVLRHLELLDEFARENIDSLYNVNLSKGRAALSATVPR
HEPPFHLDREIRLQRLSHSGSRVRVGFRLCNSTGGDCFYRGYTSGVAAVQDWYHFHYVDI
LALLPAAWEDSHGSQDGHFVLSCSYDGLDCQARQFRTFHHPTYGSCYTVDGVWTAQRPGI
THGVGLVLRVEQQPHLPLLSTLAGIRVMVHGRNHTPFLGHHSFSVRPGTEATISIREDEV
HRLGSPYGHCTAGGEGVEVELLHNTSYTRQACLVSCFQQLMVETCSCGYYLHPLPAGAEY
CSSARHPAWGHCFYRLYQDLETHRLPCTSRCPRPCRESAFKLSTGTSRWPSAKSAGWTLA
TLGEQGLPHQSHRQRSSLAKINIVYQELNYRSVEEAPVYSVPQLLSAMGSLCSLWFGASV
LSLLELLELLLDASALTLVLGGRRLRRAWFSWPRASPASGASSIKPEASQMPPPAGGTSD
DPEPSGPHLPRVMLPGVLAGVSAEESWAGPQPLETLDT
Target 5 Number of Residues 648
Target 5 Molecular Weight 70216
Target 5 Theoretical pI 7.90
Target 5 GO Classification
Function
transporter activity
ion transporter activity
ion channel activity
cation channel activity
sodium channel activity
amiloride-sensitive sodium channel activity
Process
physiological process
cellular physiological process
transport
ion transport
cation transport
monovalent inorganic cation transport
sodium ion transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 5 General Function Involved in amiloride-sensitive sodium channel activity
Target 5 Specific Function Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception
Target 5 Pathways Not Available
Target 5 Reactions Not Available
Target 5 Pfam Domain Function
Target 5 Signals
  • None
Target 5 Transmembrane Regions
  • 87-107
  • 531-551
Target 5 Essentiality Non-Essential
Target 5 GenBank ID Protein 1066457 Link Image
Target 5 UniProtKB/Swiss-Prot ID P51172 Link Image
Target 5 UniProtKB/Swiss-Prot Entry Name SCNND_HUMAN Link Image
Target 5 PDB ID Not Available
Target 5 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 5 Gene Sequence >1917 bp 
ATGGCTGAGCACCGAAGCATGGACGGGAGAATGGAAGCAGCCACACGGGGGGGCTCTCAC
CTCCAGGCTGCAGCCCAGACGCCCCCCAGGCCGGGGCCACCATCAGCACCACCACCACCA
CCCAAGGAGGGGCACCAGGAGGGGCTGGTGGAGCTGCCCGCCTCGTTCCGGGAGCTGCTC
ACCTTCTTCTGCACCAATGCCACCATCCACGGCGCCATCCGCCTGGTCTGCTCCCGCGGG
AACCGCCTCAAGACGACGTCCTGGGGGCTGCTGTCCCTGGGAGCCCTGGTCGCGCTCTGC
TGGCAGCTGGGGCTCCTCTTTGAGCGTCACTGGCACCGCCCGGTCCTCATGGCCGTCTCT
GTGCACTCGGAGCGCAAGCTGCTCCCGCTGGTCACCCTGTGTGACGGGAACCCACGTCGG
CCGAGTCCGGTCCTCCGCCATCTGGAGCTGCTGGACGAGTTTGCCAGGGAGAACATTGAC
TCCCTGTACAACGTCAACCTCAGCAAAGGCAGAGCCGCCCTCTCCGCCACTGTCCCCCGC
CACGAGCCCCCCTTCCACCTGGACCGGGAGATCCGTCTGCAGAGGCTGAGCCACTCGGGC
AGCCGGGTCAGAGTGGGGTTCAGACTGTGCAACAGCACGGGCGGCGACTGCTTTTACCGA
GGCTACACGTCAGGCGTGGCGGCTGTCCAGGACTGGTACCACTTCCACTATGTGGATATC
CTGGCCCTGCTGCCCGCGGCATGGGAGGACAGCCACGGGAGCCAGGACGGCCACTTCGTC
CTCTCCTGCAGTTACGATGGCCTGGACTGCCAGGCCCGACAGTTCCGGACCTTCCACCAC
CCCACCTACGGCAGCTGCTACACGGTCGATGGCGTCTGGACAGCTCAGCGCCCCGGCATC
ACCCACGGAGTCGGCCTGGTCCTCAGGGTTGAGCAGCAGCCTCACCTCCCTCTGCTGTCC
ACGCTGGCCGGCATCAGGGTCATGGTTCACGGCCGTAACCACACGCCCTTCCTGGGGCAC
CACAGCTTCAGCGTCCGGCCAGGGACGGAGGCCACCATCAGCATCCGAGAGGACGAGGTG
CACCGGCTCGGGAGCCCCTACGGCCACTGCACCGCCGGCGGGGAAGGCGTGGAGGTGGAG
CTGCTACACAACACCTCCTACACCAGGCAGGCCTGCCTGGTGTCCTGCTTCCAGCAGCTG
ATGGTGGAGACCTGCTCCTGTGGCTACTACCTCCACCCTCTGCCGGCGGGGGCTGAGTAC
TGCAGCTCTGCCCGGCACCCTGCCTGGGGACACTGCTTCTACCGCCTCTACCAGGACCTG
GAGACCCACCGGCTCCCCTGTACCTCCCGCTGCCCCAGGCCCTGCAGGGAGTCTGCATTC
AAGCTCTCCACTGGGACCTCCAGGTGGCCTTCCGCCAAGTCAGCTGGATGGACTCTGGCC
ACGCTAGGTGAACAGGGGCTGCCGCATCAGAGCCACAGACAGAGGAGCAGCCTGGCCAAA
ATCAACATCGTCTACCAGGAGCTCAACTACCGCTCAGTGGAGGAGGCGCCCGTGTACTCG
GTGCCGCAGCTGCTCTCCGCCATGGGCAGCCTCTACAGCCTGTGGTTTGGGGCCTCCGTC
CTCTCCCTCCTGGAGCTCCTGGAGCTGCTGCTCGATGCTTCTGCCCTCACCCTGGTGCTA
GGCGGCCGCCGGCTCCGCAGGGCGTGGTTCTCCTGGCCCAGAGCCAGCCCTGCCTCAGGG
GCGTCCAGCATCAAGCCAGAGGCCAGTCAGATGCCCCCGCCTGCAGGCGGCACGTCAGAT
GACCCGGAGCCCAGCGGGCCTCATCTCCCACGGGTGATGCTTCCAGGGGTTCTGGCGGGA
GTCTCAGCCGAAGAGAGCTGGGCTGGGCCCCAGCCCCTTGAGACTCTGGACACCTGA
Target 5 GenBank Gene ID
Target 5 GeneCard ID SCNN1D Link Image
Target 5 GenAtlas ID SCNN1D Link Image
Target 5 HGNC ID HGNC:10601 Link Image
Target 5 Chromosome Location 1
Target 5 Locus 1p36.3-p36.2
Target 5 SNPs SNPJam Report Link Image
Target 5 General References
  1. Waldmann R, Champigny G, Bassilana F, Voilley N, Lazdunski M: Molecular cloning and functional expression of a novel amiloride-sensitive Na+ channel. J Biol Chem. 1995 Nov 17;270(46):27411-4. [PubMed Link Image]
Target 5 Drug References
  1. Ji HL, Bishop LR, Anderson SJ, Fuller CM, Benos DJ: The role of Pre-H2 domains of alpha- and delta-epithelial Na+ channels in ion permeation, conductance, and amiloride sensitivity. J Biol Chem. 2004 Feb 27;279(9):8428-40. Epub 2003 Dec 2. [PubMed Link Image]
  2. Yamamura H, Ugawa S, Ueda T, Nagao M, Shimada S: Protons activate the delta-subunit of the epithelial Na+ channel in humans. J Biol Chem. 2004 Mar 26;279(13):12529-34. Epub 2004 Jan 15. [PubMed Link Image]
  3. Yamamura H, Ugawa S, Ueda T, Nagao M, Shimada S: Icilin activates the delta-subunit of the human epithelial Na+ channel. Mol Pharmacol. 2005 Oct;68(4):1142-7. Epub 2005 Jul 20. [PubMed Link Image]
  4. Yamamura H, Ugawa S, Ueda T, Shimada S: Evans blue is a specific antagonist of the human epithelial Na+ channel delta-subunit. J Pharmacol Exp Ther. 2005 Nov;315(2):965-9. Epub 2005 Aug 17. [PubMed Link Image]
  5. Ji HL, Su XF, Kedar S, Li J, Barbry P, Smith PR, Matalon S, Benos DJ: Delta-subunit confers novel biophysical features to alpha beta gamma-human epithelial sodium channel (ENaC) via a physical interaction. J Biol Chem. 2006 Mar 24;281(12):8233-41. Epub 2006 Jan 19. [PubMed Link Image]
Drug Target 6 [top]
Target 6 ID 552
Target 6 Name Amiloride-sensitive sodium channel subunit gamma
Target 6 Synonyms
  1. Epithelial Na(+) channel subunit gamma
  2. Gamma ENaC
  3. Gamma NaCH
  4. Nonvoltage-gated sodium channel 1 subunit gamma
  5. SCNEG
Target 6 Gene Name SCNN1G
Target 6 Protein Sequence >Amiloride-sensitive sodium channel gamma-subunit 
MAPGEKIKAKIKKNLPVTGPQAPTIKELMRWYCLNTNTHGCRRIVVSRGRLRRLLWIGFT
LTAVALILWQCALLVFSFYTVSVSIKVHFRKLDFPAVTICNINPYKYSTVRHLLADLEQE
TREALKSLYGFPESRKRREAESWNSVSEGKQPRFSHRIPLLIFDQDEKGKARDFFTGRKR
KVGGSIIHKASNVMHIESKQVVGFQLCSNDTSDCATYTFSSGINAIQEWYKLHYMNIMAQ
VPLEKKINMSYSAEELLVTCFFDGVSCDARNFTLFHHPMHGNCYTFNNRENETILSTSMG
GSEYGLQVILYINEEEYNPFLVSSTGAKVIIHRQDEYPFVEDVGTEIETAMVTSIGMHLT
ESFKLSEPYSQCTEDGSDVPIRNIYNAAYSLQICLHSCFQTKMVEKCGCAQYSQPLPPAA
NYCNYQQHPNWMYCYYQLHRAFVQEELGCQSVCKEACSFKEWTLTTSLAQWPSVVSEKWL
LPVLTWDQGRQVNKKLNKTDLAKLLIFYKDLNQRSIMESPANSIEMLLSNFGGQLGLWMS
CSVVCVIEIIEVFFIDFFSIIARRQWQKAKEWWAWKQAPPCPEAPRSPQGQDNPALDIDD
DLPTFNSALHLPPALGTQVPGTPPPKYNTLRLERAFSNQLTDTQMLDEL
Target 6 Number of Residues 659
Target 6 Molecular Weight 74271
Target 6 Theoretical pI 7.54
Target 6 GO Classification
Function
transporter activity
ion transporter activity
ion channel activity
cation channel activity
sodium channel activity
amiloride-sensitive sodium channel activity
Process
physiological process
cellular physiological process
transport
ion transport
cation transport
monovalent inorganic cation transport
sodium ion transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 6 General Function Involved in amiloride-sensitive sodium channel activity
Target 6 Specific Function Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception
Target 6 Pathways Not Available
Target 6 Reactions Not Available
Target 6 Pfam Domain Function
Target 6 Signals
  • None
Target 6 Transmembrane Regions
  • 56-76
  • 542-562
Target 6 Essentiality Non-Essential
Target 6 GenBank ID Protein 1004273 Link Image
Target 6 UniProtKB/Swiss-Prot ID P51170 Link Image
Target 6 UniProtKB/Swiss-Prot Entry Name SCNNG_HUMAN Link Image
Target 6 PDB ID Not Available
Target 6 Cellular Location
  • Cell membrane
  • apical cell membrane
  • multi- pass membrane protein. Apical membrane of epithelial cel
Target 6 Gene Sequence >1950 bp 
ATGGCCCCCGGGGAGAAGATCAAAGCCAAAATCAAGAAGAATCTGCCCGTGACGGGCCCT
CAGGCGCCGACCATTAAAGAGCTGATGCGGTGGTACTGCCTCAACACCAACACCCATGGC
TGTCGCCGCATCGTGGTGTCCCGCGGCCGTCTGCGCCGCCTCCTCTGGATCGGGTTCACA
CTGACTGCCGTGGCCCTCATCCTCTGGCAGTGCGCCCTCCTCGTCTTCTCCTTCTATACT
GTCTCAGTTTCCATCAAAGTCCACTTCCGGAAGCTGGATTTTCCTGCAGTCACCATCTGC
AACATCAACCCCTACAAGTACAGCACCGTTCGCCACCTTCTAGCTGACTTGGAACAGGAG
ACCAGAGAGGCCCTGAAGTCCCTGTATGGCTTTCCAGAGTCCCGGAAGCGCCGAGAGGCG
GAGTCCTGGAACTCCGTCTCAGAGGGAAAGCAGCCTAGATTCTCCCACCGGATTCCGCTG
CTGATCTTTGATCAGGATGAGAAGGGCAAGGCCAGGGACTTCTTCACAGGGAGGAAGCGG
AAAGTCGGCGGTAGCATCATTCACAAGGCTTCAAATGTCATGCACATCGAGTCCAAGCAA
GTGGTGGGATTCCAACTGTGCTCAAATGACACCTCCGACTGTGCCACCTACACCTTCAGC
TCGGGAATCAATGCCATTCAGGAGTGGTATAAGCTACACTACATGAACATCATGGCACAG
GTGCCTCTGGAGAAGAAAATCAACATGAGCTATTCTGCTGAGGAGCTGCTGGTGACCTGC
TTCTTTGATGGAGTGTCCTGTGATGCCAGGAATTTCACGCTTTTCCACCACCCGATGCAT
GGGAATTGCTATACTTTCAACAACAGAGAAAATGAGACCATTCTCAGCACCTCCATGGGG
GGCAGCGAATATGGGCTGCAAGTCATTTTGTACATAAACGAAGAGGAATACAACCCATTC
CTCGTGTCCTCCACTGGAGCTAAGGTGATCATCCATCGGCAGGATGAGTATCCCTCCGTC
GAAGATGTGGGAACAGAGATTGAGACAACAATGGTCACCTCTATAGGAATGCACCTGACA
GAGTCCTTCAAGCTGAGTGAGCCCTCCAGTCAGTGCACGGAGGGCGGGAGTGACGTGCCA
ATCAGGAACATCTACAACGCTGCCTACTCGCTCCAGATCTGCCTTCATTCATGCTTCCAG
ACAAAGATGGTGGAGAAATGTGGGTGTGCCCAGTACAGCCAGCCTCTACCTCCTGCAGCC
AACTACTGCAACTACCAGCAGCACCCCAACTGGATGTATTGTTACTACCAACTGCATCGA
GCCTTTGTCCAGGAAGAGCTGGGCTGCCAGTCTGTGTGCAAGGAAGCCTGCCGCTTTAAA
GAGTGGACACTAACCACAAGCCTGGCACAATGGCCATCTGTGGTTTCGGAGAAGTGGTTG
CTGCCTGTTCTCACTTGGGACCAAGGCCGGCAAGTAAACAAAAAGCTCAACAAGACAGAC
TTGGCCAAACTCTTGATATTCTACAAAGACCTGAACCAGAGATCCATCATGGAGAGCCCA
GCCAACAGTATTGAGATGCTTCTGTCCAACTTCGGCGGTCAGCTGGGCCTGTGGATGAGC
TGCTCTGTTGTCTGCGTCATCGAGATCATCGAGGTCTTCTTCATTGACTTCTTCTCTATC
ATTGCCCGCCGCCAGTGGCAGAAAGCCAAGGAGTGGTGGGCCTGGAAACAGGCTCCCCCA
TGTCCAGAAGCTCCCCGTAGCCCACAGGGCCAGGACAATCCAGCCCTGGATATAGACGAT
GACCTACCCACTTTCAACTCTGCTTTGCACCTGCCTCCAGCCCTAGGAACCCAAGTGCCC
GGCACACCGCCCCCCAAATACAATACCTTGCGCTTGGAGAGGGCCTTTTCCAACCAGCTC
ACAGATACCCAGATGCTGGATGAGCTCTGA
Target 6 GenBank Gene ID
Target 6 GeneCard ID SCNN1G Link Image
Target 6 GenAtlas ID SCNN1G Link Image
Target 6 HGNC ID HGNC:10602 Link Image
Target 6 Chromosome Location 16
Target 6 Locus 16p12
Target 6 SNPs SNPJam Report Link Image
Target 6 General References
  1. Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A: Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis. Nat Genet. 1999 Jul;22(3):239-47. [PubMed Link Image]
  2. Arai K, Zachman K, Shibasaki T, Chrousos GP: Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential? J Clin Endocrinol Metab. 1999 Jul;84(7):2434-7. [PubMed Link Image]
  3. McDonald FJ, Western AH, McNeil JD, Thomas BC, Olson DR, Snyder PM: Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel. Am J Physiol Renal Physiol. 2002 Sep;283(3):F431-6. [PubMed Link Image]
  4. Voilley N, Bassilana F, Mignon C, Merscher S, Mattei MG, Carle GF, Lazdunski M, Barbry P: Cloning, chromosomal localization, and physical linkage of the beta and gamma subunits (SCNN1B and SCNN1G) of the human epithelial amiloride-sensitive sodium channel. Genomics. 1995 Aug 10;28(3):560-5. [PubMed Link Image]
  5. Hansson JH, Nelson-Williams C, Suzuki H, Schild L, Shimkets R, Lu Y, Canessa C, Iwasaki T, Rossier B, Lifton RP: Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. Nat Genet. 1995 Sep;11(1):76-82. [PubMed Link Image]
  6. McDonald FJ, Price MP, Snyder PM, Welsh MJ: Cloning and expression of the beta- and gamma-subunits of the human epithelial sodium channel. Am J Physiol. 1995 May;268(5 Pt 1):C1157-63. [PubMed Link Image]
  7. Thomas CP, Doggett NA, Fisher R, Stokes JB: Genomic organization and the 5' flanking region of the gamma subunit of the human amiloride-sensitive epithelial sodium channel. J Biol Chem. 1996 Oct 18;271(42):26062-6. [PubMed Link Image]
  8. Pirozzi G, McConnell SJ, Uveges AJ, Carter JM, Sparks AB, Kay BK, Fowlkes DM: Identification of novel human WW domain-containing proteins by cloning of ligand targets. J Biol Chem. 1997 Jun 6;272(23):14611-6. [PubMed Link Image]
Target 6 Drug References
  1. Viemann M, Peter M, Lopez-Siguero JP, Simic-Schleicher G, Sippell WG: Evidence for genetic heterogeneity of pseudohypoaldosteronism type 1: identification of a novel mutation in the human mineralocorticoid receptor in one sporadic case and no mutations in two autosomal dominant kindreds. J Clin Endocrinol Metab. 2001 May;86(5):2056-9. [PubMed Link Image]
  2. Iwai N, Baba S, Mannami T, Katsuya T, Higaki J, Ogihara T, Ogata J: Association of sodium channel gamma-subunit promoter variant with blood pressure. Hypertension. 2001 Jul;38(1):86-9. [PubMed Link Image]
  3. Yamagata T, Yamagata Y, Nishimoto T, Nakanishi M, Nakanishi H, Minakata Y, Mune M, Yukawa S: The impact of phorbol ester on the regulation of amiloride-sensitive epithelial sodium channel in alveolar type ii epithelial cells. Exp Lung Res. 2002 Oct-Nov;28(7):543-62. [PubMed Link Image]
  4. Akcay A, Yavuz T, Semiz S, Bundak R, Demirdoven M: Pseudohypoaldosteronism type 1 and respiratory distress syndrome. J Pediatr Endocrinol Metab. 2002 Nov-Dec;15(9):1557-61. [PubMed Link Image]
  5. Ludwig M, Bidlingmaier F, Reissinger A: Pseudohypoaldosteronism type 1 and the genes encoding prostasin, alpha-spectrin, and Nedd4. Int J Mol Med. 2004 Dec;14(6):1101-4. [PubMed Link Image]
Drug Target 7 [top]
Target 7 ID 749
Target 7 Name Amiloride-sensitive cation channel 1, neuronal
Target 7 Synonyms
  1. ASIC2
  2. Acid-sensing ion channel 2
  3. Amiloride-sensitive brain sodium channel
  4. Amiloride-sensitive cation channel neuronal 1
  5. BNC1
  6. BNaC1
  7. Brain sodium channel 1
  8. Mammalian degenerin homolog
Target 7 Gene Name ACCN1
Target 7 Protein Sequence >Amiloride-sensitive cation channel 1, neuronal 
MDLKESPSEGSLQPSSIQIFANTSTLHGIRHIFVYGPLTIRRVLWAVAFVGSLGLLLVES
SERVSYYFSYQHVTKVDEVVAQSLVFPAVTLCNLNGFRFSRLTTNDLYHAGELLALLDVN
LQIPDPHLADPSVLEALRQKANFKHYKPKQFSMLEFLHRVGHDLKDMMLYCKFKGQECGH
QDFTTVFTKYGKCYMFNSGEDGKPLLTTVKGGTGNGLEIMLDIQQDEYLPIWGETEETTF
EAGVKVQIHSQSEPPFIQELGFGVAPGFQTFVATQEQRLTYLPPPWGECRSSEMGLDFFP
VYSITACRIDCETRYIVENCNCRMVHMPGDAPFCTPEQHKECAEPALGLLAEKDSNYCLC
RTPCNLTRYNKELSMVKIPSKTSAKYLEKKFNKSEKYISENILVLDIFFEALNYETIEQK
KAYEVAALLGDIGGQMGLFIGASILTILELFDYIYELIKEKLLDLLGKEEDEGSHDENVS
TCDTMPNHSETISHTVNVPLQTTLGTLEEIAC
Target 7 Number of Residues 520
Target 7 Molecular Weight 57710
Target 7 Theoretical pI 4.84
Target 7 GO Classification
Function
transporter activity
ion transporter activity
ion channel activity
cation channel activity
sodium channel activity
amiloride-sensitive sodium channel activity
Process
physiological process
cellular physiological process
transport
ion transport
cation transport
monovalent inorganic cation transport
sodium ion transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 7 General Function Involved in amiloride-sensitive sodium channel activity
Target 7 Specific Function Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Li(+) and K(+). Generates a biphasic current with a fast inactivating and a slow sustained phase. Heteromeric channel assembly seems to modulate
Target 7 Pathways Not Available
Target 7 Reactions Not Available
Target 7 Pfam Domain Function
Target 7 Signals
  • None
Target 7 Transmembrane Regions
  • 38-58
  • 428-448
Target 7 Essentiality Non-Essential
Target 7 GenBank ID Protein 1256017 Link Image
Target 7 UniProtKB/Swiss-Prot ID Q16515 Link Image
Target 7 UniProtKB/Swiss-Prot Entry Name ACCN1_HUMAN Link Image
Target 7 PDB ID Not Available
Target 7 Cellular Location
  • Cell membrane
  • multi-pass membrane protein. Localized at the plasma membrane of neurons, in the soma
Target 7 Gene Sequence >1539 bp 
ATGGACCTCAAGGAAAGCCCCAGTGAGGGCAGCCTGCAACCTTCTAGCATCCAGATCTTT
GCCAACACCTCCACCCTCCATGGCATCCGCCACATCTTCGTGTATGGGCCGCTGACCATC
CGGCGTGTGCTGTGGGCAGTGGCCTTCGTGGGCTCTCTGGGCCTGCTGCTGGTGGAGAGC
TCTGAGAGGGTGTCCTACTACTTCTCCTACCAGCATGTCACTAAGGTGGACGAAGTGGTG
GCTCAAAGCCTGGTCTTCCCAGCTGTGACCCTCTGTAACCTCAATGGCTTCCGGTTCTCC
AGGCTCACCACCAACGACCTGTACCATGCTGGGGAGCTGCTGGCCCTGCTGGATGTCAAC
CTGCAGATCCCGGACCCCCATCTGGCTGACCCCTCCGTGCTGGAGGCCCTGCGGCAGAAG
GCCAACTTCAAGCACTACAAACCCAAGCAGTTCAGCATGCTGGAGTTCCTGCACCGTGTG
GGCCATGACCTGAAGGATATGATGCTCTACTGCAAGTTCAAAGGGCAGGAGTGCGGCCAC
CAAGACTTCACCACAGTGTTTACAAAATATGGGAAGTGTTACATGTTTAACTCAGGCGAG
GATGGCAAACCTCTGCTCACCACGGTCAAGGGGGGGACAGGCAACGGGCTGGAGATCATG
CTGGACATTCAGCAGGATGAGTACCTGCCCATCTGGGGAGAGACAGAGGAAACGACATTT
GAAGCAGGAGTGAAAGTTCAGATCCACAGTCAGTCTGAGCCACCTTTCATCCAAGAGCTG
GGCTTTGGGGTGGCTCCAGGGTTCCAGACCTTTGTGGCCACACAGGAGCAGAGGCTCACA
TACCTGCCCCCACCGTGGGGTGAGTGCCGATCCTCAGAGATGGGCCTCGACTTTTTTCCT
GTTTACAGCATCACCGCCTGTAGGATTGACTGTGAGACCCGCTACATTGTGGAAAACTGC
AACTGCCGCATGGTTCACATGCCAGGGGATGCCCCTTTTTGTACCCCTGAGCAGCACAAG
GAGTGTGCAGAGCCTGCCCTAGGTCTGTTGGCGGAAAAGGACAGCAATTACTGTCTCTGC
AGGACACCCTGCAACCTAACCCGCTACAACAAAGAGCTCTCCATGGTGAAGATCCCCAGC
AAGACATCAGCCAAGTACCTTGAGAAGAAATTTAACAAATCAGAAAAATATATCTCAGAG
AACATCCTTGTTCTGGATATATTTTTTGAAGCTCTCAATTATGAGACAATTGAACAGAAG
AAGGCGTATGAAGTTGCTGCCTTACTTGGTGATATTGGTGGTCAGATGGGATTGTTCATT
GGTGCTAGTATCCTTACAATACTAGAGCTCTTTGATTATATTTATGAGCTGATCAAAGAG
AAGCTATTAGACCTGCTTGGCAAAGAGGAGGACGAAGGGAGCCACGATGAGAATGTGAGT
ACTTGTGACACAATGCCAAACCACTCTGAAACCATCAGTCACGCTGTGAACGTGCCCCTG
CAGACGACCCTGGGGACCTTGGAGGAGATTGCCTGCTGA
Target 7 GenBank Gene ID
Target 7 GeneCard ID ACCN1 Link Image
Target 7 GenAtlas ID ACCN1 Link Image
Target 7 HGNC ID HGNC:99 Link Image
Target 7 Chromosome Location 17
Target 7 Locus 17q12
Target 7 SNPs SNPJam Report Link Image
Target 7 General References
  1. Hruska-Hageman AM, Wemmie JA, Price MP, Welsh MJ: Interaction of the synaptic protein PICK1 (protein interacting with C kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel). Biochem J. 2002 Feb 1;361(Pt 3):443-50. [PubMed Link Image]
  2. Price MP, Snyder PM, Welsh MJ: Cloning and expression of a novel human brain Na+ channel. J Biol Chem. 1996 Apr 5;271(14):7879-82. [PubMed Link Image]
  3. Waldmann R, Champigny G, Voilley N, Lauritzen I, Lazdunski M: The mammalian degenerin MDEG, an amiloride-sensitive cation channel activated by mutations causing neurodegeneration in Caenorhabditis elegans. J Biol Chem. 1996 May 3;271(18):10433-6. [PubMed Link Image]
  4. Garcia-Anoveros J, Derfler B, Neville-Golden J, Hyman BT, Corey DP: BNaC1 and BNaC2 constitute a new family of human neuronal sodium channels related to degenerins and epithelial sodium channels. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1459-64. [PubMed Link Image]
Target 7 Drug References
  1. Berdiev BK, Xia J, McLean LA, Markert JM, Gillespie GY, Mapstone TB, Naren AP, Jovov B, Bubien JK, Ji HL, Fuller CM, Kirk KL, Benos DJ: Acid-sensing ion channels in malignant gliomas. J Biol Chem. 2003 Apr 25;278(17):15023-34. Epub 2003 Feb 12. [PubMed Link Image]
  2. Ugawa S, Yamamoto T, Ueda T, Ishida Y, Inagaki A, Nishigaki M, Shimada S: Amiloride-insensitive currents of the acid-sensing ion channel-2a (ASIC2a)/ASIC2b heteromeric sour-taste receptor channel. J Neurosci. 2003 May 1;23(9):3616-22. [PubMed Link Image]
  3. Ugawa S: Identification of sour-taste receptor genes. Anat Sci Int. 2003 Dec;78(4):205-10. [PubMed Link Image]
  4. Peng BG, Ahmad S, Chen S, Chen P, Price MP, Lin X: Acid-sensing ion channel 2 contributes a major component to acid-evoked excitatory responses in spiral ganglion neurons and plays a role in noise susceptibility of mice. J Neurosci. 2004 Nov 10;24(45):10167-75. [PubMed Link Image]
  5. Vila-Carriles WH, Kovacs GG, Jovov B, Zhou ZH, Pahwa AK, Colby G, Esimai O, Gillespie GY, Mapstone TB, Markert JM, Fuller CM, Bubien JK, Benos DJ: Surface expression of ASIC2 inhibits the amiloride-sensitive current and migration of glioma cells. J Biol Chem. 2006 Jul 14;281(28):19220-32. Epub 2006 May 16. [PubMed Link Image]
Drug Target 8 [top]
Target 8 ID 827
Target 8 Name Sodium/hydrogen exchanger 1
Target 8 Synonyms
  1. APNH
  2. NHE-1
  3. Na(+)/H(+) exchanger 1
  4. Na(+)/H(+)antiporter, amiloride-sensitive
  5. Solute carrier family 9 member 1
Target 8 Gene Name SLC9A1
Target 8 Protein Sequence >Sodium/hydrogen exchanger 1 
MVLRSGICGLSPHRIFPSLLVVVALVGLLPVLRSHGLQLSPTASTIRSSEPPRERSIGDV
TTAPPEVTPESRPVNHSVTDHGMKPRKAFPVLGIDYTHVRTPFEISLWILLACLMKIGFH
VIPTISSIVPESCLLIVVGLLVGGLIKGVGETPPFLQSDVFFLFLLPPIILDAGYFLPLR
QFTENLGTILIFAVVGTLWNAFFLGGLMYAVCLVGGEQINNIGLLDNLLFGSIISAVDPV
AVLAVFEEIHINELLHILVFGESLLNDAVTVVLYHLFEEFANYEHVGIVDIFLGFLSFFV
VALGGVLVGVVYGVIAAFTSRFTSHIRVIEPLFVFLYSYMAYLSAELFHLSGIMALIASG
VVMRPYVEANISHKSHTTIKYFLKMWSSVSETLIFIFLGVSTVAGSHHWNWTFVISTLLF
CLIARVLGVLGLTWFINKFRIVKLTPKDQFIIAYGGLRGAIAFSLGYLLDKKHFPMCDLF
LTAIITVIFFTVFVQGMTIRPLVDLLAVKKKQETKRSINEEIHTQFLDHLLTGIEDICGH
YGHHHWKDKLNRFNKKYVKKCLIAGERSKEPQLIAFYHKMEMKQAIELVESGGMGKIPSA
VSTVSMQNIHPKSLPSERILPALSKDKEEEIRKILRNNLQKTRQRLRSYNRHTLVADPYE
EAWNQMLLRRQKARQLEQKINNYLTVPAHKLDSPTMSRARIGSDPLAYEPKEDLPVITID
PASPQSPESVDLVNEELKGKVLGLSRDPAKVAEEDEDDDGGIMMRSKETSSPGTDDVFTP
APSDSPSSQRIQRCLSDPGPHPEPGEGEPFFPKGQ
Target 8 Number of Residues 828
Target 8 Molecular Weight 90764
Target 8 Theoretical pI 7.22
Target 8 GO Classification
Function
monovalent inorganic cation transporter activity
hydrogen ion transporter activity
monovalent cation:proton antiporter activity
sodium:hydrogen antiporter activity
transporter activity
ion transporter activity
cation transporter activity
solute:cation antiporter activity
solute:hydrogen antiporter activity
Process
cellular physiological process
transport
ion transport
cation transport
monovalent inorganic cation transport
sodium ion transport
physiological process
homeostasis
ion homeostasis
regulation of pH
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 8 General Function Inorganic ion transport and metabolism
Target 8 Specific Function Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction
Target 8 Pathways Not Available
Target 8 Reactions Not Available
Target 8 Pfam Domain Function
Target 8 Signals
  • None
Target 8 Transmembrane Regions
  • 16-35
  • 108-127
  • 130-149
  • 155-174
  • 192-211
  • 228-247
  • 257-276
  • 295-315
  • 339-358
  • 387-406
  • 411-430
  • 481-500
Target 8 Essentiality Non-Essential
Target 8 GenBank ID Protein 178753 Link Image
Target 8 UniProtKB/Swiss-Prot ID P19634 Link Image
Target 8 UniProtKB/Swiss-Prot Entry Name SL9A1_HUMAN Link Image
Target 8 PDB ID 1Y4E Link Image
Target 8 PDB File Show
Target 8 3D Structure
Target 8 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 8 Gene Sequence >2448 bp 
ATGGTTCTGCGGTCTGGCATCTGTGGCCTCTCTCCACATCGGATCTTCCCTTCCTTACTC
GTGGTGGTTGCTTTGGTGGGGCTGCTGCCTGTTCTCAGGAGCCATGGCCTCCAGCTCAGC
CCAACTGCCAGCACCATTCGAAGCTCAGAGCCACCACGAGAACGCTCGATTGGGGATGTC
ACCACCGCTCCACCGGAGGTCACCCCAGAGAGCCGCCCTGTTAATCATTCCGTCACTGAT
CATGGCATGAAGCCGCGCAAGGCCTTTCCAGTCCTGGGCATCGACTACACACACGTGCGC
ACCCCCTTCGAGATCTCCCTCTGGATCCTTCTGGCCTGCCTCATGAAGATAGGTTTCCAT
GTGATCCCCACTATCTCAAGCATCGTCCCGGAGAGCTGCCTGCTGATCGTGGTGGGGCTG
CTGGTGGGGGGCCTGATCAAGGGTGTAGGCGAGACACCCCCCTTCCTGCAGTCCGACGTC
TTCTTCCTCTTCCTGCTGCCGCCCATCATCCTGGATGCGGGCTACTTCCTGCCACTGCGG
CAGTTCACAGAAAACCTGGGCACCATCCTGATCTTTGCCGTGGTGGGCACGCTGTGGAAC
GCCTCCTTCCTGGGCGGCCTCATGTACGCCGTGTGCCTGGTGGGCGGTGAGCAGATCAAC
AACATCGGCCTCCTGGACAACCTGCTCTTCGGCAGCATCATCTCGGCCGTGGACCCCGTG
GCGGTTCTGGCTGTCTTTGAGGAAATTCACATCAATGAGCTGCTGCACATCCTTGTTTTT
GGGGAGTCCTTGCTCAATGACGCCGTCACTGTGGTCCTGTATCACCTCTTTGAGGAGTTT
GCCAACTACGAACACTGTGGCATCGTGGACATCTTCCTCGGCTTCCTGAGCTTCTTCGTG
GTGGCCCTGGGCGGGGTGCTTGTGGGCGTGGTCTACGGGGTCATCGCAGCCTTCACCTCC
CGATTTACCTCCCACATCCGGGTCATCGAGCCGCTCTTCGTCTTCCTCTACAGCTACATG
GCCTACTTGTCAGCCGAGCTCTTCCACCTGTCAGGCATCATGGCGCTCATAGCCTCAGGA
GTGGTGATGCGCCCCTATGTGGAGGCCAACATCTCCCACAAGTCCCACACCACCATCAAA
TACTTCCTGAAGATGTGGAGCAGCGTCAGCGAGACCCTCATCTTCATCTTCCTCGGCGTC
TCCACGGTGGCCGGCTCCCACCACTGGAACTGGACCTTCGTCATCAGCACCCTGCTCTTC
TGCCTCATCGCCCGCGTGCTGGGGGTGCTGGGCCTGACCTGGTTCATCAACAAGTTCCGT
ATCGTGAAGCTGACCCCCAAGGACCAGTTCATCATCGCCTATGGGGGCCTGCGAGGGGCC
ATCGCCTTCTCTCTGGGCTACCTCCTGGACAAGAAGCACTTCCCCATGTGTGACCTGTTC
CTCACTGCCATCATCACTGTCATCTTCTTCACCGTCTTTGTGCAGGGCATGACCATTCGG
CCCCTGGTAGACCTGTTGGCTGTGAAGAAAAAGCAAGAGACGAAGCGCTCCATCAACGAA
GAGATCCACACACAGTTCCTGGACCACCTTCTGACAGGCATCGAAGACATCTGTGGCCAC
TACGGTCACCACCACTGGAAGGACAAGCTCAACCGGTTTAATAAGAAATATGTGAAGAAG
TGTCTGATAGCTGGCGAGCGCTCCAAGGAGCCCCAGCTCATTGCCTTCTACCACAAGATG
GAGATGAAGCAGGCCATCGAGCTGGTGGAGAGCGGGGGCATGGGCAAGATCCCCTCTGCC
GTCTCCACCGTCTCCATGCAGAACATCCACCCCAAGTCCCTGCCTTCCGAGCGCATCCTG
CCAGCACTGTCCAAGGACAACGAGGAGGAGATCCGCAAAATCCTGAGGAACAACTTGCAG
AAGACCAGGCAGCGGCTGCGGTCCTACAACAGACACACGCTGGTGGCAGACCCCTACGAG
GAAGCCTGGAACCAGATGCTGCTCCGGAGGCAGAAGGCCCGGCAGCTGGAGCAGAAGATC
AACAACTACCTGACGGTGCCAGCCCACAAGCTGGACTCACCCACCATGTCTCGGGCCCGC
ATCGGCTCAGACCCACTGGCCTATGAGCCGAAGGAGGACCTGCCTGTCATCACCATCGAC
CCGGCTTCCCCGCAGTCACCCGAGTCTGTGGACCTGGTGAATGAGGAGCTGAAGGGCAAA
GTCTTAGGGTTGAGCCGGGATCCTGCAAAGGTGGCTGAGGAGGACGAGGACGACGATGGG
GGCATCATGATGCGGAGCAAGGAGACTTCGTCCCCAGGAACCGACGATGTCTTCACCCCC
GCGCCCAGTGACAGCCCCAGCTCCCAGAGGATACAGCGCTGCCTCAGTGACCCAGGCCCA
CACCCTGAGCCTGGGGAGGGAGAACCGTCCTTCCCCAAGGGGCAGTAA
Target 8 GenBank Gene ID
Target 8 GeneCard ID SLC9A1 Link Image
Target 8 GenAtlas ID SLC9A1 Link Image
Target 8 HGNC ID HGNC:11071 Link Image
Target 8 Chromosome Location 1
Target 8 Locus 1p36.1-p35
Target 8 SNPs SNPJam Report Link Image
Target 8 General References
  1. Garden OA, Musk P, Worthington-White DA, Dewey MJ, Rich IN: Silent polymorphisms within the coding region of human sodium/hydrogen exchanger isoform-1 cDNA in peripheral blood mononuclear cells of leukemia patients: A comparison with healthy controls. Cancer Genet Cytogenet. 2000 Jul 1;120(1):37-43. [PubMed Link Image]
  2. Pang T, Su X, Wakabayashi S, Shigekawa M: Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers. J Biol Chem. 2001 May 18;276(20):17367-72. Epub 2001 Feb 28. [PubMed Link Image]
  3. Pang T, Wakabayashi S, Shigekawa M: Expression of calcineurin B homologous protein 2 protects serum deprivation-induced cell death by serum-independent activation of Na+/H+ exchanger. J Biol Chem. 2002 Nov 15;277(46):43771-7. Epub 2002 Sep 10. [PubMed Link Image]
  4. Tse CM, Ma AI, Yang VW, Watson AJ, Levine S, Montrose MH, Potter J, Sardet C, Pouyssegur J, Donowitz M: Molecular cloning and expression of a cDNA encoding the rabbit ileal villus cell basolateral membrane Na+/H+ exchanger. EMBO J. 1991 Aug;10(8):1957-67. [PubMed Link Image]
  5. Sardet C, Counillon L, Franchi A, Pouyssegur J: Growth factors induce phosphorylation of the Na+/H+ antiporter, glycoprotein of 110 kD. Science. 1990 Feb 9;247(4943):723-6. [PubMed Link Image]
  6. Sardet C, Franchi A, Pouyssegur J: Molecular cloning, primary structure, and expression of the human growth factor-activatable Na+/H+ antiporter. Cell. 1989 Jan 27;56(2):271-80. [PubMed Link Image]
  7. Fliegel L, Dyck JR, Wang H, Fong C, Haworth RS: Cloning and analysis of the human myocardial Na+/H+ exchanger. Mol Cell Biochem. 1993 Aug 25;125(2):137-43. [PubMed Link Image]
Target 8 Drug References
  1. Lee MG, Ahn W, Choi JY, Luo X, Seo JT, Schultheis PJ, Shull GE, Kim KH, Muallem S: Na(+)-dependent transporters mediate HCO(3)(-) salvage across the luminal membrane of the main pancreatic duct. J Clin Invest. 2000 Jun;105(11):1651-8. [PubMed Link Image]
  2. Konstantinou-Tegou A, Kaloyianni M, Bourikas D, Koliakos G: The effect of leptin on Na(+)-H(+) antiport (NHE 1) activity of obese and normal subjects erythrocytes. Mol Cell Endocrinol. 2001 Oct 25;183(1-2):11-8. [PubMed Link Image]
  3. Serrani RE, Mujica G, Gioia IA, Corchs JL: Neonatal red blood cells: amiloride-insensitive Na+-H+ transport isoform would express Na+-Li+ exchange. Acta Physiol Pharmacol Bulg. 2000;25(3-4):71-4. [PubMed Link Image]
  4. Cuthbert AW, Supuran CT, MacVinish LJ: Bicarbonate-dependent chloride secretion in Calu-3 epithelia in response to 7,8-benzoquinoline. J Physiol. 2003 Aug 15;551(Pt 1):79-92. Epub 2003 Jul 18. [PubMed Link Image]
  5. Furukawa O, Bi LC, Guth PH, Engel E, Hirokawa M, Kaunitz JD: NHE3 inhibition activates duodenal bicarbonate secretion in the rat. Am J Physiol Gastrointest Liver Physiol. 2004 Jan;286(1):G102-9. Epub 2003 Jul 24. [PubMed Link Image]
Drug Target 9 [top]
Target 9 ID 1074
Target 9 Name Urokinase-type plasminogen activator
Target 9 Synonyms
  1. EC 3.4.21.73
  2. U-plasminogen activator
  3. Urokinase-type plasminogen activator precursor
  4. uPA
Target 9 Gene Name PLAU
Target 9 Protein Sequence >Urokinase-type plasminogen activator precursor 
MRALLARLLLCVLVVSDSKGSNELHQVPSNCDCLNGGTCVSNKYFSNIHWCNCPKKFGGQ
HCEIDKSKTCYEGNGHFYRGKASTDTMGRPCLPWNSATVLQQTYHAHRSDALQLGLGKHN
YCRNPDNRRRPWCYVQVGLKPLVQECMVHDCADGKKPSSPPEELKFQCGQKTLRPRFKII
GGEFTTIENQPWFAAIYRRHRGGSVTYVCGGSLMSPCWVISATHCFIDYPKKEDYIVYLG
RSRLNSNTQGEMKFEVENLILHKDYSADTLAHHNDIALLKIRSKEGRCAQPSRTIQTICL
PSMYNDPQFGTSCEITGFGKENSTDYLYPEQLKMTVVKLISHRECQQPHYYGSEVTTKML
CAADPQWKTDSCQGDSGGPLVCSLQGRMTLTGIVSWGRGCALKDKPGVYTRVSHFLPWIR
SHTKEENGLAL
Target 9 Number of Residues 438
Target 9 Molecular Weight 48526
Target 9 Theoretical pI 8.48
Target 9 GO Classification
Function
catalytic activity
hydrolase activity
peptidase activity
endopeptidase activity
serine-type endopeptidase activity
Process
physiological process
metabolism
macromolecule metabolism
protein metabolism
cellular protein metabolism
proteolysis
Component
Not Available
Target 9 General Function Involved in chemotaxis and signal transduction activity
Target 9 Specific Function Specifically cleave the zymogen plasminogen to form the active enzyme plasmin
Target 9 Pathways Not Available
Target 9 Reactions
  • Specific cleavage of Arg!Val bond in plasminogen to form plasmin
Target 9 Pfam Domain Function
Target 9 Signals
  • 1-20
Target 9 Transmembrane Regions
  • None
Target 9 Essentiality Non-Essential
Target 9 GenBank ID Protein 1834524 Link Image
Target 9 UniProtKB/Swiss-Prot ID P00749 Link Image
Target 9 UniProtKB/Swiss-Prot Entry Name UROK_HUMAN Link Image
Target 9 PDB ID 1VJA Link Image
Target 9 PDB File Show
Target 9 3D Structure
Target 9 Cellular Location
  • Secreted protein
Target 9 Gene Sequence >1296 bp 
ATGAGAGCCCTGCTGGCGCGCCTGCTTCTCTGCGTCCTGGTCGTGAGCGACTCCAAAGGC
AGCAATGAACTTCATCAAGTTCCATCGAACTGTGACTGTCTAAATGGAGGAACATGTGTG
TCCAACAAGTACTTCTCCAACATTCACTGGTGCAACTGCCCAAAGAAATTCGGAGGGCAG
CACTGTGAAATAGATAAGTCAAAAACCTGCTATGAGGGGAATGGTCACTTTTACCGAGGA
AAGGCCAGCACTGACACCATGGGCCGGCCCTGCCTGCCCTGGAACTCTGCCACTGTCCTT
CAGCAAACGTACCATGCCCACAGATCTGATGCTCTTCAGCTGGGCCTGGGGAAACATAAT
TACTGCAGGAACCCAGACAACCGGAGGCGACCCTGGTGCTATGTGCAGGTGGGCCTAAAG
CCGCTTGTCCAAGAGTGCATGGTGCATGACTGCGCAGATGGAAAAAAGCCCTCCTCTCCT
CCAGAAGAATTAAAATTTCAGTGTGGCCAAAAGACTCTGAGGCCCCGCTTTAAGATTATT
GGGGGAGAATTCACCACCATCGAGAACCAGCCCTGGTTTGCGGCCATCTACAGGAGGCAC
CGGGGGGGCTCTGTCACCTACGTGTGTGGAGGCAGCCTCATGAGCCCTTGCTGGGTGATC
AGCGCCACACACTGCTTCATTGATTACCCAAAGAAGGAGGACTACATCGTCTACCTGGGT
CGCTCAAGGCTTAACTCCAACACGCAAGGGGAGATGAAGTTTGAGGTGGAAAACCTCATC
CTACACAAGGACTACAGCGCTGACACGCTTGCTCACCACAACGACATTGCCTTGCTGAAG
ATCCGTTCCAAGGAGGGCAGGTGTGCGCAGCCATCCCGGACTATACAGACCATCTGCCTG
CCCTCGATGTATAACGATCCCCAGTTTGGCACAAGCTGTGAGATCACTGGCTTTGGAAAA
GAGAATTCTACCGACTATCTCTATCCGGAGCAGCTGAAAATGACTGTTGTGAAGCTGATT
TCCCACCGGGAGTGTCAGCAGCCCCACTACTACGGCTCTGAAGTCACCACCAAAATGCTG
TGTGCTGCTGACCCACAGTGGAAAACAGATTCCTGCCAGGGAGACTCAGGGGGACCCCTC
GTCTGTTCCCTCCAAGGCCGCATGACTTTGACTGGAATTGTGAGCTGGGGCCGTGGATGT
GCCCTGAAGGACAAGCCAGGCGTCTACACGAGAGTCTCACACTTCTTACCCTGGATCCGC
AGTCACACCAAGGAAGAGAATGGCCTGGCCCTCTGA
Target 9 GenBank Gene ID
Target 9 GeneCard ID PLAU Link Image
Target 9 GenAtlas ID PLAU Link Image
Target 9 HGNC ID HGNC:9052 Link Image
Target 9 Chromosome Location 10
Target 9 Locus 10q24
Target 9 SNPs SNPJam Report Link Image
Target 9 General References
  1. Behrendt N, Jensen ON, Engelholm LH, Mortz E, Mann M, Dano K: A urokinase receptor-associated protein with specific collagen binding properties. J Biol Chem. 2000 Jan 21;275(3):1993-2002. [PubMed Link Image]
  2. Sperl S, Jacob U, Arroyo de Prada N, Sturzebecher J, Wilhelm OG, Bode W, Magdolen V, Huber R, Moroder L: (4-aminomethyl)phenylguanidine derivatives as nonpeptidic highly selective inhibitors of human urokinase. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5113-8. [PubMed Link Image]
  3. Liu CX, Li Y, Obermoeller-McCormick LM, Schwartz AL, Bu G: The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein. J Biol Chem. 2001 Aug 3;276(31):28889-96. Epub 2001 May 30. [PubMed Link Image]
  4. Li X, Smith RA, Dobson CM: Sequential 1H NMR assignments and secondary structure of the kringle domain from urokinase. Biochemistry. 1992 Oct 13;31(40):9562-71. [PubMed Link Image]
  5. Nagai M, Hiramatsu R, Kaneda T, Hayasuke N, Arimura H, Nishida M, Suyama T: Molecular cloning of cDNA coding for human preprourokinase. Gene. 1985;36(1-2):183-8. [PubMed Link Image]
  6. Oswald RE, Bogusky MJ, Bamberger M, Smith RA, Dobson CM: Dynamics of the multidomain fibrinolytic protein urokinase from two-dimensional NMR. Nature. 1989 Feb 9;337(6207):579-82. [PubMed Link Image]
  7. Riccio A, Grimaldi G, Verde P, Sebastio G, Boast S, Blasi F: The human urokinase-plasminogen activator gene and its promoter. Nucleic Acids Res. 1985 Apr 25;13(8):2759-71. [PubMed Link Image]
  8. Jacobs P, Cravador A, Loriau R, Brockly F, Colau B, Chuchana P, van Elsen A, Herzog A, Bollen A: Molecular cloning, sequencing, and expression in Escherichia coli of human preprourokinase cDNA. DNA. 1985 Apr;4(2):139-46. [PubMed Link Image]
  9. Verde P, Stoppelli MP, Galeffi P, Di Nocera P, Blasi F: Identification and primary sequence of an unspliced human urokinase poly(A)+ RNA. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4727-31. [PubMed Link Image]
  10. Schaller J, Nick H, Rickli EE, Gillessen D, Lergier W, Studer RO: Human low-molecular-weight urinary urokinase. Partial characterization and preliminary sequence data of the two polypeptide chains. Eur J Biochem. 1982 Jul;125(2):251-7. [PubMed Link Image]
  11. 6754569 Gunzler WA, Steffens GJ, Otting F, Kim SM, Frankus E, Flohe L: The primary structure of high molecular mass urokinase from human urine. The complete amino acid sequence of the A chain. Hoppe Seylers Z Physiol Chem. 1982 Oct;363(10):1155-65.
  12. 6754572 Steffens GJ, Gunzler WA, Otting F, Frankus E, Flohe L: The complete amino acid sequence of low molecular mass urokinase from human urine. Hoppe Seylers Z Physiol Chem. 1982 Sep;363(9):1043-58.
  13. 8107091 Li X, Bokman AM, Llinas M, Smith RA, Dobson CM: Solution structure of the kringle domain from urokinase-type plasminogen activator. J Mol Biol. 1994 Feb 4;235(5):1548-59.
  14. 8591045 Spraggon G, Phillips C, Nowak UK, Ponting CP, Saunders D, Dobson CM, Stuart DI, Jones EY: The crystal structure of the catalytic domain of human urokinase-type plasminogen activator. Structure. 1995 Jul 15;3(7):681-91.
  15. 8652631 Yoshimoto M, Ushiyama Y, Sakai M, Tamaki S, Hara H, Takahashi K, Sawasaki Y, Hanada K: Characterization of single chain urokinase-type plasminogen activator with a novel amino-acid substitution in the kringle structure. Biochim Biophys Acta. 1996 Mar 7;1293(1):83-9.
  16. 9065988 Conne B, Berczy M, Belin D: Detection of polymorphisms in the human urokinase-type plasminogen activator gene. Thromb Haemost. 1997 Mar;77(3):434-5.
  17. 9151681 Franco P, Iaccarino C, Chiaradonna F, Brandazza A, Iavarone C, Mastronicola MR, Nolli ML, Stoppelli MP: Phosphorylation of human pro-urokinase on Ser138/303 impairs its receptor-dependent ability to promote myelomonocytic adherence and motility. J Cell Biol. 1997 May 5;137(3):779-91.
  18. 9194591 Turkmen B, Schmitt M, Schmalfeldt B, Trommler P, Hell W, Creutzburg S, Graeff H, Magdolen V: Mutational analysis of the genes encoding urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in advanced ovarian cancer. Electrophoresis. 1997 May;18(5):686-9.
Target 9 Drug References
  1. Vakili J, Standker L, Detheux M, Vassart G, Forssmann WG, Parmentier M: Urokinase plasminogen activator and plasmin efficiently convert hemofiltrate CC chemokine 1 into its active. J Immunol. 2001 Sep 15;167(6):3406-13. [PubMed Link Image]
  2. Jankun J, Skrzypczak-Jankun E: Binding site of amiloride to urokinase plasminogen activator depends on species. Int J Mol Med. 2001 Oct;8(4):365-71. [PubMed Link Image]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  4. Luikart S, Masri M, Wahl D, Hinkel T, Beck JM, Gyetko MR, Gupta P, Oegema T: Urokinase is required for the formation of mactinin, an alpha-actinin fragment that promotes monocyte/macrophage maturation. Biochim Biophys Acta. 2002 Aug 19;1591(1-3):99-107. [PubMed Link Image]
  5. Chen YX, O'Brien ER: Ethyl isopropyl amiloride inhibits smooth muscle cell proliferation and migration by inducing apoptosis and antagonizing urokinase plasminogen activator activity. Can J Physiol Pharmacol. 2003 Jul;81(7):730-9. [PubMed Link Image]
  6. Cejkova J, Cejka C, Zvarova J: Effects of inhibition of urokinase-type plasminogen activator (u-PA) by amiloride in the cornea and tear fluid of eyes irradiated with UVB. Acta Histochem. 2005;107(1):77-86. Epub 2005 Mar 4. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.