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26  structures 8165  species 0  interactions 45701  sequences 355  architectures

Family: Na_H_Exchanger (PF00999)

Summary: Sodium/hydrogen exchanger family

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Sodium/hydrogen exchanger family Provide feedback

Na/H antiporters are key transporters in maintaining the pH of actively metabolising cells. The molecular mechanisms of antiport are unclear. These antiporters contain 10-12 transmembrane regions (M) at the amino-terminus and a large cytoplasmic region at the carboxyl terminus. The transmembrane regions M3-M12 share identity with other members of the family. The M6 and M7 regions are highly conserved. Thus, this is thought to be the region that is involved in the transport of sodium and hydrogen ions. The cytoplasmic region has little similarity throughout the family.

Literature references

  1. Dibrov P, Fliegel L; , FEBS Lett 1998;424:1-5.: Comparative molecular analysis of Na+/H+ exchangers: a unified model for Na+/H+ antiport? PUBMED:9537504 EPMC:9537504

  2. Orlowski J, Grinstein S; , J Biol Chem 1997;272:22373-22376.: Na+/H+ exchangers of mammalian cells. PUBMED:9278382 EPMC:9278382

  3. Numata M, Petrecca K, Lake N, Orlowski J; , J Biol Chem 1998;273:6951-6959.: Identification of a mitochondrial Na+/H+ exchanger. PUBMED:9507001 EPMC:9507001

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR006153

Sodium proton exchangers (NHEs) constitute a large family of integral membrane protein transporters that are responsible for the counter-transport of protons and sodium ions across lipid bilayers [ PUBMED:12027219 , PUBMED:12502567 ]. These proteins are found in organisms across all domains of life. In archaea, bacteria, yeast and plants, these exchangers provide increased salt tolerance by removing sodium in exchanger for extracellular protons. In mammals they participate in the regulation of cell pH, volume, and intracellular sodium concentration, as well as for the reabsorption of NaCl across renal, intestinal, and other epithelia [ PUBMED:16734752 , PUBMED:17071327 , PUBMED:16513813 , PUBMED:11187762 ]. Human NHE is also involved in heart disease, cell growth and in cell differentiation [ PUBMED:17218973 ]. The removal of intracellular protons in exchange for extracellular sodium effectively eliminates excess acid from actively metabolising cells. In mammalian cells, NHE activity is found in both the plasma membrane and inner mitochondrial membrane. To date, nine mammalian isoforms have been identified (designated NHE1-NHE9) [ PUBMED:9278382 , PUBMED:9507001 ]. These exchangers are highly-regulated (glyco)phosphoproteins, which, based on their primary structure, appear to contain 10-12 membrane-spanning regions (M) at the N terminus and a large cytoplasmic region at the C terminus. The transmembrane regions M3-M12 share identity with other members of the family. The M6 and M7 regions are highly conserved. Thus, this is thought to be the region that is involved in the transport of sodium and hydrogen ions. The cytoplasmic region has little similarity throughout the family. There is some evidence that the exchangers may exist in the cell membrane as homodimers, but little is currently known about the mechanism of their antiport [ PUBMED:9537504 ].

This entry represents a number of cation/proton exchangers, including Na+/H+ exchangers, K+/H+ exchangers and Na+(K+,Li+,Rb+)/H+ exchangers.

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 13 members:

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


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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

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Seed source: Pfam-B_312 (release 3.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Finn RD , Bateman A
Number in seed: 58
Number in full: 45701
Average length of the domain: 366.80 aa
Average identity of full alignment: 17 %
Average coverage of the sequence by the domain: 63.43 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.2 26.2
Trusted cut-off 26.2 26.2
Noise cut-off 26.1 26.1
Model length: 381
Family (HMM) version: 23
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Species distribution

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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_Exchanger domain has been found. There are 26 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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