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Identification
HMDB Protein ID HMDBP06889
Secondary Accession Numbers
  • 12508
Name Sodium/hydrogen exchanger 4
Synonyms
  1. NHE-4
  2. Na(+)/H(+) exchanger 4
  3. Solute carrier family 9 member 4
Gene Name SLC9A4
Protein Type Unknown
Biological Properties
General Function Involved in solute:hydrogen antiporter activity
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. May play a specialized role in the kidney in rectifying cell volume in response to extreme fluctuations of hyperosmolar-stimulated cell shrinkage. Is relatively amiloride and ethylisopropylamiloride (EIPA) insensitive. Can be activated under conditions of hyperosmolar-induced cell shrinkage in a sustained intracellular acidification-dependence manner. Activated by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in a sustained intracellular acidification-dependence manner. Affects potassium/proton exchange as well as sodium/proton and lithium/proton exchange. In basolateral cell membrane, participates in homeostatic control of intracellular pH, and may play a role in proton extrusion in order to achieve transepithelial HCO3(-) secretion. In apical cell membrane may be involved in mediating sodium absorption. Requires for normal levels of gastric acid secretion, secretory membrane development, parietal cell maturation and/or differentiation and at least secondarily for chief cell differentiation
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
monovalent cation:hydrogen antiporter activity
sodium:hydrogen antiporter activity
solute:cation antiporter activity
solute:hydrogen antiporter activity
transmembrane transporter activity
substrate-specific transmembrane transporter activity
ion transmembrane transporter activity
cation transmembrane transporter activity
inorganic cation transmembrane transporter activity
monovalent inorganic cation transmembrane transporter activity
hydrogen ion transmembrane transporter activity
transporter activity
Process
cation homeostasis
monovalent inorganic cation homeostasis
regulation of ph
sodium ion transport
establishment of localization
transport
biological regulation
transmembrane transport
monovalent inorganic cation transport
ion transport
cation transport
regulation of biological quality
homeostatic process
chemical homeostasis
ion homeostasis
Cellular Location
  1. Multi-pass membrane protein
  2. Multi-pass membrane protein
  3. Multi-pass membrane protein
  4. Basolateral cell membrane
  5. Apical cell membrane
  6. Cytoplasmic granule membrane
Gene Properties
Chromosome Location Chromosome:2
Locus 2q12.1
SNPs SLC9A4
Gene Sequence
>2397 bp
ATGGCTCTGCAGATGTTCGTGACTTACAGTCCTTGGAATTGTTTGCTACTGCTAGTGGCT
CTTGAGTGTTCTGAAGCATCTTCTGATTTGAATGAATCTGCAAATTCCACTGCTCAGTAT
GCATCTAACGCTTGGTTTGCTGCTGCCAGCTCAGAGCCAGAGGAAGGGATATCTGTTTTT
GAACTGGATTATGACTATGTGCAAATTCCTTATGAGGTCACTCTCTGGATACTTCTAGCA
TCCCTTGCAAAAATAGGCTTCCACCTCTACCACAGGCTGCCAGGCCTCATGCCAGAAAGC
TGCCTCCTCATCCTGGTGGGGGCGCTGGTGGGCGGCATCATCTTCGGCACCGACCACAAA
TCGCCTCCGGTCATGGACTCCAGCATCTACTTCCTGTATCTCCTGCCACCCATCGTTCTG
GAGGGCGGCTACTTCATGCCCACCCGGCCCTTCTTTGAGAACATCGGCTCCATCCTGTGG
TGGGCAGTATTGGGGGCCCTGATCAACGCCTTGGGCATTGGCCTCTCCCTCTACCTCATC
TGCCAGGTGAAGGCCTTTGGCCTGGGCGACGTCAACCTGCTGCAGAACCTGCTGTTCGGC
AGCCTGATCTCCGCCGTGGACCCAGTGGCCGTGCTAGCCGTGTTTGAGGAAGCGCGCGTG
AACGAGCAGCTCTACATGATGATCTTTGGGGAGGCCCTGCTCAATGATGGCATTACTGTG
GTCTTATACAATATGTTAATTGCCTTTACAAAGATGCATAAATTTGAAGACATAGAAACT
GTCGACATTTTGGCTGGATGTGCCCGATTCATCGTTGTGGGGCTTGGAGGGGTATTGTTT
GGCATCGTTTTTGGATTTATTTCTGCATTTATCACACGTTTCACTCAGAATATCTCTGCA
ATTGAGCCACTCATCGTCTTCATGTTCAGCTATTTGTCTTACTTAGCTGCTGAAACCCTC
TATCTCTCCGGCATCCTGGCAATCACAGCCTGCGCAGTAACAATGAAAAAGTACGTGGAA
GAAAACGTGTCCCAGACATCATACACGACCATCAAGTACTTCATGAAGATGCTGAGCAGC
GTCAGCGAGACCTTGATCTTCATCTTCATGGGTGTGTCCACTGTGGGCAAGAATCACGAG
TGGAACTGGGCCTTCATCTGCTTCACCCTGGCCTTCTGCCAAATCTGGAGAGCCATCAGC
GTATTTGCTCTCTTCTATATCAGTAACCAGTTTCGGACTTTCCCCTTCTCCATCAAGGAC
CAGTGCATCATTTTCTACAGTGGTGTTCGAGGAGCTGGAAGTTTTTCACTTGCATTTTTG
CTTCCTCTGTCTCTTTTTCCTAGGAAGAAAATGTTTGTCACTGCTACTCTAGTAGTTATA
TACTTTACTGTATTTATTCAGGGAATCACAGTTGGCCCTCTGGTCAGGTACCTGGATGTT
AAAAAAACCAATAAAAAAGAATCCATCAATGAAGAGCTTCATATTCGTCTGATGGATCAC
TTAAAGGCTGGAATCGAAGATGTGTGTGGGCACTGGAGTCACTACCAAGTGAGAGACAAG
TTTAAGAAGTTTGATCATAGATACTTACGGAAAATCCTCATCAGAAAGAACCTACCCAAA
TCAAGCATTGTTTCTTTGTACAAGAAGCTGGAAATGAAGCAAGCCATCGAGATGGTGGAG
ACTGGGATACTGAGCTCTACAGCTTTCTCCATACCCCATCAGGCCCAGAGGATACAAGGA
ATCAAAAGACTTTCCCCTGAAGATGTGGAGTCCATAAGGGACATTCTGACATCCAACATG
TACCAAGTTCGGCAAAGGACCCTGTCCTACAACAAATACAACCTCAAACCCCAAACAAGT
GAGAAGCAGGCTAAAGAGATTCTGATCCGCCGCCAGAACACCTTAAGGGAGAGCATGAGG
AAAGGTCACAGCCTGCCCTGGGGAAAGCCGGCTGGCACCAAGAATATCCGCTACCTCTCC
TACCCCTACGGGAATCCTCAGTCTGCAGGAAGAGACACAAGGGCTGCTGGGTTCTCAGAT
GATGACAGCAGTGATCCAGGATCCCCATCCATCACGTTCAGCGCATGCTCTCGGATAGGG
TCACTTCAGAAGCAAGAGGCACAAGAAATAATACCAATGAAGAGCCTACACAGAGGAAGG
AAGGCATTCAGCTTTGGTTATCAAAGAAACACAAGCCAAGAAGAGTACTTGGGTGGAGTA
AGGAGGGTGGCCTTAAGACCCAAACCTCTGTTTCATGCAGTGGATGAGGAGGGTGAGTCT
GGAGGGGAGAGTGAGGGCAAGGCCTCTTTGGTTGAGGTTCGGTCGAGGTGGACAGCTGAC
CATGGACACGGCAGGGACCATCACAGGTCCCATAGTCCTTTGCTCCAAAAAAAATAG
Protein Properties
Number of Residues 798
Molecular Weight 89813.4
Theoretical pI 8.72
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 95-115
  • 128-148
  • 155-175
  • 197-217
  • 227-247
  • 271-291
  • 305-325
  • 357-373
  • 385-405
  • 451-471
Protein Sequence
>Sodium/hydrogen exchanger 4
MALQMFVTYSPWNCLLLLVALECSEASSDLNESANSTAQYASNAWFAAASSEPEEGISVF
ELDYDYVQIPYEVTLWILLASLAKIGFHLYHRLPGLMPESCLLILVGALVGGIIFGTDHK
SPPVMDSSIYFLYLLPPIVLEGGYFMPTRPFFENIGSILWWAVLGALINALGIGLSLYLI
CQVKAFGLGDVNLLQNLLFGSLISAVDPVAVLAVFEEARVNEQLYMMIFGEALLNDGITV
VLYNMLIAFTKMHKFEDIETVDILAGCARFIVVGLGGVLFGIVFGFISAFITRFTQNISA
IEPLIVFMFSYLSYLAAETLYLSGILAITACAVTMKKYVEENVSQTSYTTIKYFMKMLSS
VSETLIFIFMGVSTVGKNHEWNWAFICFTLAFCQIWRAISVFALFYISNQFRTFPFSIKD
QCIIFYSGVRGAGSFSLAFLLPLSLFPRKKMFVTATLVVIYFTVFIQGITVGPLVRYLDV
KKTNKKESINEELHIRLMDHLKAGIEDVCGHWSHYQVRDKFKKFDHRYLRKILIRKNLPK
SSIVSLYKKLEMKQAIEMVETGILSSTAFSIPHQAQRIQGIKRLSPEDVESIRDILTSNM
YQVRQRTLSYNKYNLKPQTSEKQAKEILIRRQNTLRESMRKGHSLPWGKPAGTKNIRYLS
YPYGNPQSAGRDTRAAGFSDDDSSDPGSPSITFSACSRIGSLQKQEAQEIIPMKSLHRGR
KAFSFGYQRNTSQEEYLGGVRRVALRPKPLFHAVDEEGESGGESEGKASLVEVRSRWTAD
HGHGRDHHRSHSPLLQKK
GenBank ID Protein 148727259
UniProtKB/Swiss-Prot ID Q6AI14
UniProtKB/Swiss-Prot Entry Name SL9A4_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_001011552.3
GeneCard ID SLC9A4
GenAtlas ID SLC9A4
HGNC ID HGNC:11077
References
General References
  1. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [PubMed:15815621 ]
  2. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  3. Denis NJ, Vasilescu J, Lambert JP, Smith JC, Figeys D: Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry. Proteomics. 2007 Mar;7(6):868-74. [PubMed:17370265 ]