Sodium/hydrogen exchanger 3

Details

Name
Sodium/hydrogen exchanger 3
Synonyms
  • Na(+)/H(+) exchanger 3
  • NHE-3
  • NHE3
  • Solute carrier family 9 member 3
Gene Name
SLC9A3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052127|Sodium/hydrogen exchanger 3
MWGLGARGPDRGLLLALALGGLARAGGVEVEPGGAHGESGGFQVVTFEWAHVQDPYVIAL
WILVASLAKIGFHLSHKVTSVVPESALLIVLGLVLGGIVWAADHIASFTLTPTVFFFYLL
PPIVLDAGYFMPNRLFFGNLGTILLYAVVGTVWNAATTGLSLYGVFLSGLMGDLQIGLLD
FLLFGSLMAAVDPVAVLAVFEEVHVNEVLFIIVFGESLLNDAVTVVLYNVFESFVALGGD
NVTGVDCVKGIVSFFVVSLGGTLVGVVFAFLLSLVTRFTKHVRIIEPGFVFIISYLSYLT
SEMLSLSAILAITFCGICCQKYVKANISEQSATTVRYTMKMLASSAETIIFMFLGISAVN
PFIWTWNTAFVLLTLVFISVYRAIGVVLQTWLLNRYRMVQLEPIDQVVLSYGGLRGAVAF
ALVVLLDGDKVKEKNLFVSTTIIVVFFTVIFQGLTIKPLVQWLKVKRSEHREPRLNEKLH
GRAFDHILSAIEDISGQIGHNYLRDKWSHFDRKFLSRVLMRRSAQKSRDRILNVFHELNL
KDAISYVAEGERRGSLAFIRSPSTDNVVNVDFTPRSSTVEASVSYLLRENVSAVCLDMQS
LEQRRRSIRDAEDMVTHHTLQQYLYKPRQEYKHLYSRHELTPTEDEKQDREIFHRTMRKR
LESFKSTKLGLNQNKKAAKLYKRERAQKRRNSSIPNGKLPMESPAQNFTIKEKDLELSDT
EEPPNYDEEMSGGIEFLASVTKDTASDSPAGIDNPVFSPDEALDRSLLARLPPWLSPGET
VVPSQRARTQIPYSPGTFCRLMPFRLSSKSVDSFLQADGPEERPPAALPESTHM
Number of residues
834
Molecular Weight
92853.665
Theoretical pI
Not Available
GO Classification
Functions
PDZ domain binding / potassium / sodium
Processes
ion transport / potassium ion transmembrane transport / regulation of intracellular pH / sodium ion import across plasma membrane
Components
apical plasma membrane / brush border / brush border membrane / cell surface / extracellular exosome / integral component of membrane / plasma membrane
General 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 (PubMed:26358773). Plays an important role in signal transduction.
Specific Function
Pdz domain binding
Pfam Domain Function
Transmembrane Regions
80-99 113-133 140-160 181-202 211-232 253-274 291-309 341-362 370-390 436-456
Cellular Location
Apical cell membrane
Gene sequence
>lcl|BSEQ0052128|Sodium/hydrogen exchanger 3 (SLC9A3)
ATGTGGGGACTCGGGGCCCGGGGCCCCGACCGGGGGCTGCTGCTGGCGCTGGCGCTGGGC
GGGCTGGCGCGGGCCGGGGGCGTCGAGGTGGAGCCCGGCGGCGCGCACGGCGAGAGCGGG
GGCTTCCAGGTGGTCACCTTCGAGTGGGCCCACGTGCAGGATCCCTACGTCATCGCGCTC
TGGATCCTCGTGGCCAGCTTGGCCAAGATCGGGTTCCACCTGTCCCACAAGGTCACCAGC
GTGGTTCCCGAGAGCGCCCTGCTCATCGTGCTGGGCCTGGTGCTGGGCGGCATCGTCTGG
GCGGCCGACCACATCGCGTCCTTCACACTGACGCCCACCGTCTTCTTCTTCTACCTGCTG
CCCCCCATCGTGCTGGACGCCGGCTACTTCATGCCCAACCGCCTCTTCTTCGGCAACCTG
GGGACCATCCTGTTGTACGCCGTCGTGGGTACCGTGTGGAACGCGGCCACCACCGGGCTG
TCCCTCTACGGCGTCTTCCTCAGTGGGCTCATGGGCGACCTGCAGATTGGGCTGCTGGAC
TTCCTCCTGTTTGGCAGCCTCATGGCGGCTGTGGACCCGGTGGCCGTCCTGGCCGTGTTT
GAGGAGGTCCATGTCAACGAGGTCCTGTTCATCATCGTCTTCGGGGAGTCGCTGCTGAAC
GACGCAGTCACCGTGGTTCTGTACAATGTGTTTGAATCTTTCGTGGCGCTGGGAGGTGAC
AACGTGACTGGCGTGGACTGCGTGAAGGGCATAGTGTCCTTCTTCGTGGTGAGCCTGGGG
GGCACGCTGGTGGGGGTGGTCTTCGCCTTCCTGCTGTCGCTGGTGACGCGCTTCACCAAG
CATGTGCGTATCATCGAGCCCGGCTTCGTGTTCATCATCTCCTACCTGTCCTACCTGACG
TCCGAGATGCTGTCGCTGTCGGCCATCCTCGCCATCACCTTCTGTGGCATCTGCTGTCAG
AAGTATGTGAAGGCCAACATCTCGGAGCAGTCGGCCACCACCGTGCGCTACACCATGAAG
ATGCTGGCCAGCAGCGCCGAGACCATCATCTTCATGTTCCTGGGTATCTCGGCCGTGAAC
CCGTTCATCTGGACCTGGAACACGGCCTTCGTGCTCCTGACGCTGGTCTTCATCTCCGTG
TACCGGGCCATCGGTGTGGTCCTGCAGACCTGGCTTCTGAACCGCTACCGCATGGTGCAG
CTGGAGCCCATTGACCAGGTGGTCCTGTCCTACGGGGGCCTGCGCGGGGCCGTGGCCTTT
GCCCTGGTGGTGCTTCTGGATGGAGACAAGGTCAAGGAGAAGAACCTGTTCGTCAGCACC
ACCATCATCGTAGTGTTCTTCACCGTCATCTTCCAGGGCCTGACCATCAAGCCTCTGGTG
CAGTGGCTGAAGGTGAAGAGGAGCGAGCACCGGGAACCTCGGCTCAACGAGAAGCTGCAC
GGGCGCGCTTTCGACCACATCCTCTCGGCCATCGAGGACATATCCGGACAGATCGGGCAC
AATTATCTCAGAGACAAGTGGTCCCACTTCGACAGGAAGTTCCTCAGCAGGGTCCTCATG
AGACGGTCGGCCCAGAAGTCTCGAGACCGGATCCTGAATGTCTTCCACGAGCTGAACCTG
AAGGATGCCATCAGCTACGTGGCTGAGGGAGAGCGCCGCGGGTCCCTGGCCTTCATCCGC
TCCCCCAGCACCGACAACGTGGTCAACGTGGACTTCACGCCACGATCGTCCACCGTGGAG
GCCTCTGTCTCCTACCTCCTGAGAGAAAATGTCAGCGCTGTCTGCCTGGACATGCAGTCT
CTGGAGCAGCGACGGCGGAGCATCCGGGACGCGGAGGACATGGTCACGCACCACACGCTA
CAGCAGTACCTGTACAAGCCGCGGCAGGAGTACAAGCATCTGTACAGCCGACACGAGCTC
ACGCCCACGGAGGACGAGAAACAGGACCGGGAAATCTTCCACAGGACCATGCGGAAGCGC
CTGGAGTCCTTCAAGTCGACCAAGCTGGGGCTCAACCAGAACAAGAAGGCGGCCAAGCTG
TACAAGCGGGAGCGTGCCCAGAAGCGGAGAAACAGCAGCATCCCCAATGGGAAGCTGCCC
ATGGAGAGCCCTGCGCAGAATTTCACCATCAAGGAGAAAGACTTGGAACTTTCAGACACC
GAGGAGCCCCCCAACTATGATGAGGAGATGAGTGGGGGGATCGAGTTCCTGGCTAGTGTC
ACCAAGGACACAGCGTCCGACTCCCCTGCAGGAATTGACAACCCTGTGTTTTCTCCGGAC
GAGGCCCTGGACCGCAGCCTCCTGGCCAGGCTGCCGCCCTGGCTGTCTCCCGGGGAGACG
GTGGTCCCCTCGCAGAGGGCCCGCACGCAGATTCCCTACTCTCCCGGCACCTTCTGCCGC
CTGATGCCCTTCCGCCTCAGCAGCAAGTCCGTGGACTCCTTCCTGCAGGCAGACGGCCCC
GAGGAGCGGCCCCCCGCCGCCCTCCCCGAGTCCACACACATGTGA
Chromosome Location
5
Locus
5p15.33
External Identifiers
ResourceLink
UniProtKB IDP48764
UniProtKB Entry NameSL9A3_HUMAN
HGNC IDHGNC:11073
General References
  1. Brant SR, Yun CH, Donowitz M, Tse CM: Cloning, tissue distribution, and functional analysis of the human Na+/N+ exchanger isoform, NHE3. Am J Physiol. 1995 Jul;269(1 Pt 1):C198-206. doi: 10.1152/ajpcell.1995.269.1.C198. [Article]
  2. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Zachos NC, Hodson C, Kovbasnjuk O, Li X, Thelin WR, Cha B, Milgram S, Donowitz M: Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4) dependent mechanism. Cell Physiol Biochem. 2008;22(5-6):693-704. doi: 10.1159/000185553. Epub 2008 Dec 9. [Article]
  5. He P, Zhang H, Yun CC: IRBIT, inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with IP3, binds Na+/H+ exchanger NHE3 and activates NHE3 activity in response to calcium. J Biol Chem. 2008 Nov 28;283(48):33544-53. doi: 10.1074/jbc.M805534200. Epub 2008 Sep 30. [Article]
  6. He P, Klein J, Yun CC: Activation of Na+/H+ exchanger NHE3 by angiotensin II is mediated by inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with IP3 (IRBIT) and Ca2+/calmodulin-dependent protein kinase II. J Biol Chem. 2010 Sep 3;285(36):27869-78. doi: 10.1074/jbc.M110.133066. Epub 2010 Jun 28. [Article]
  7. Janecke AR, Heinz-Erian P, Yin J, Petersen BS, Franke A, Lechner S, Fuchs I, Melancon S, Uhlig HH, Travis S, Marinier E, Perisic V, Ristic N, Gerner P, Booth IW, Wedenoja S, Baumgartner N, Vodopiutz J, Frechette-Duval MC, De Lafollie J, Persad R, Warner N, Tse CM, Sud K, Zachos NC, Sarker R, Zhu X, Muise AM, Zimmer KP, Witt H, Zoller H, Donowitz M, Muller T: Reduced sodium/proton exchanger NHE3 activity causes congenital sodium diarrhea. Hum Mol Genet. 2015 Dec 1;24(23):6614-23. doi: 10.1093/hmg/ddv367. Epub 2015 Sep 10. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB11761Tenapanorapproved, investigationalyesinhibitorDetails