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11  structures 3150  species 0  interactions 4911  sequences 19  architectures

Family: Na_H_antiport_1 (PF06965)

Summary: Na+/H+ antiporter 1

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This is the Wikipedia entry entitled "Sodium/proton antiporter 1". More...

Sodium/proton antiporter 1 Edit Wikipedia article

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "Sodium–hydrogen antiporter 1". More...

Sodium–hydrogen antiporter 1 Edit Wikipedia article

Protein SLC9A1 PDB 2bec.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesSLC9A1, APNH, NHE-1, NHE1, PPP1R143, LIKNS, Sodium–hydrogen antiporter 1, solute carrier family 9 member A1
External IDsOMIM: 107310 MGI: 102462 HomoloGene: 20660 GeneCards: SLC9A1
Gene location (Human)
Chromosome 1 (human)
Chr.Chromosome 1 (human)[1]
Chromosome 1 (human)
Genomic location for SLC9A1
Genomic location for SLC9A1
Band1p36.11Start27,098,809 bp[1]
End27,166,981 bp[1]
RNA expression pattern
PBB GE SLC9A1 209453 at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 1: 27.1 – 27.17 MbChr 4: 133.37 – 133.42 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

The sodium-hydrogen antiporter 1 (NHE-1) also known as sodium/hydrogen exchanger 1 or SLC9A1 (SoLute Carrier family 9A1) is an isoform of sodium–hydrogen antiporter that in humans is encoded by the SLC9A1 gene.[5]


The Na+/H+ antiporter (SLC9A1) is a ubiquitous membrane-bound enzyme involved in volume- and pH-regulation of vertebrate cells. It is inhibited by the non-specific diuretic drug amiloride and activated by a variety of signals including growth factors, mitogens, neurotransmitters, tumor promoters, and others.[6]


Sodium–hydrogen antiporter 1 has been shown to interact with carbonic anhydrase II[7] and CHP.[8][9][10] It is also the target of the experimental drug rimeporide, which is being developed for the treatment of Duchenne muscular dystrophy.[11]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000090020 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028854 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Fliegel L, Dyck JR, Wang H, Fong C, Haworth RS (August 1993). "Cloning and analysis of the human myocardial Na+/H+ exchanger". Molecular and Cellular Biochemistry. 125 (2): 137–43. doi:10.1007/BF00936442. PMID 8283968.
  6. ^ Cardone RA, Alfarouk KO, Elliott RL, Alqahtani SS, Ahmed SB, Aljarbou AN, et al. (July 2019). "The Role of Sodium Hydrogen Exchanger 1 in Dysregulation of Proton Dynamics and Reprogramming of Cancer Metabolism as a Sequela". International Journal of Molecular Sciences. 20 (15): 3694. doi:10.3390/ijms20153694. PMC 6696090. PMID 31357694.
  7. ^ Li X, Alvarez B, Casey JR, Reithmeier RA, Fliegel L (September 2002). "Carbonic anhydrase II binds to and enhances activity of the Na+/H+ exchanger". The Journal of Biological Chemistry. 277 (39): 36085–91. doi:10.1074/jbc.M111952200. PMID 12138085.
  8. ^ Inoue H, Nakamura Y, Nagita M, Takai T, Masuda M, Nakamura N, Kanazawa H (February 2003). "Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein, is expressed in intestinal epithelium". Biological & Pharmaceutical Bulletin. 26 (2): 148–55. doi:10.1248/bpb.26.148. PMID 12576672.
  9. ^ Lin X, Barber DL (October 1996). "A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange". Proceedings of the National Academy of Sciences of the United States of America. 93 (22): 12631–6. Bibcode:1996PNAS...9312631L. doi:10.1073/pnas.93.22.12631. PMC 38044. PMID 8901634.
  10. ^ Pang T, Su X, Wakabayashi S, Shigekawa M (May 2001). "Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers". The Journal of Biological Chemistry. 276 (20): 17367–72. doi:10.1074/jbc.M100296200. PMID 11350981.
  11. ^ Spreitzer, Helmut (26 May 2015). "Rimeporide". Österreichische Apothekerzeitung (in German). 69 (11): 12.

Further reading

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Na+/H+ antiporter 1 Provide feedback

This family contains a number of bacterial Na+/H+ antiporter 1 proteins. These are integral membrane proteins that catalyse the exchange of H+ for Na+ in a manner that is highly dependent on the pH [1].

Literature references

  1. Karpel R, Alon T, Glaser G, Schuldiner S, Padan E; , J Biol Chem 1991;266:21753-21759.: Expression of a sodium proton antiporter (NhaA) in Escherichia coli is induced by Na+ and Li+ ions. PUBMED:1657980 EPMC:1657980

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR004670

NhaA is a sodium ion/proton antiporter that uses the proton electrochemical gradient to expel sodium ions from the cytoplasm and functions primarily in the adaptation to high salinity at alkaline pH. NhaA is also believed to be responsible for adaptation to alkaline pH when sodium is available. NhaA is one of the three known sodium ion/proton antiporters in Escherichia coli along with NhaB and ChaA, though there are other mechanisms for Na+ extrusion such as NDH-I complicating the determination of the precise roles of each of the transporters [ PUBMED:19448069 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan CPA_AT (CL0064), which has the following description:

This Clan contains transporter proteins that belong to the CPA superfamily and AT superfamily according to TCDB [1].

The clan contains the following 15 members:

Asp-Al_Ex Cons_hypoth698 DUF3100 DUF819 Glt_symporter KdgT LrgB Lys_export Mem_trans Na_H_antiport_1 Na_H_Exchanger OAD_beta SBF SBF_like Sbt_1


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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Curation and family details

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Seed source: Pfam-B_1828 (release 10.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Vella Briffa B
Number in seed: 337
Number in full: 4911
Average length of the domain: 376.10 aa
Average identity of full alignment: 40 %
Average coverage of the sequence by the domain: 87.16 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.5 23.5
Trusted cut-off 23.7 23.7
Noise cut-off 23.0 22.8
Model length: 374
Family (HMM) version: 15
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Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Na_H_antiport_1 domain has been found. There are 11 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
P13738 View 3D Structure Click here