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26  structures 8165  species 0  interactions 45701  sequences 355  architectures

Family: Na_H_Exchanger (PF00999)

Summary: Sodium/hydrogen exchanger family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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.

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

Alignments

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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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(58)
Full
(45701)
Representative proteomes UniProt
(167732)
RP15
(6088)
RP35
(20836)
RP55
(42854)
RP75
(70982)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(58)
Full
(45701)
Representative proteomes UniProt
(167732)
RP15
(6088)
RP35
(20836)
RP55
(42854)
RP75
(70982)
Alignment:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(58)
Full
(45701)
Representative proteomes UniProt
(167732)
RP15
(6088)
RP35
(20836)
RP55
(42854)
RP75
(70982)
Raw Stockholm Download   Download   Download   Download   Download      
Gzipped Download   Download   Download   Download   Download      

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

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.

Curation View help on the curation process

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
Download: download the raw HMM for this family

Species distribution

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Selections

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Structures

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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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
A0A075W8S1 View 3D Structure Click here
A0A0B4K6G5 View 3D Structure Click here
A0A0G2K3D4 View 3D Structure Click here
A0A0G2KZI8 View 3D Structure Click here
A0A0N7KIB8 View 3D Structure Click here
A0A0P0V9Q3 View 3D Structure Click here
A0A0P0WGH1 View 3D Structure Click here
A0A0P0WVY4 View 3D Structure Click here
A0A0P0XIF9 View 3D Structure Click here
A0A0P0XNN5 View 3D Structure Click here
A0A0P0XYV8 View 3D Structure Click here
A0A0P0Y603 View 3D Structure Click here
A0A0P0YC61 View 3D Structure Click here
A0A0R0EEL1 View 3D Structure Click here
A0A0R0EUU1 View 3D Structure Click here
A0A0R0EWH5 View 3D Structure Click here
A0A0R0G3I0 View 3D Structure Click here
A0A0R0G8S3 View 3D Structure Click here
A0A0R0G8S7 View 3D Structure Click here
A0A0R0GIK0 View 3D Structure Click here
A0A0R0GK75 View 3D Structure Click here
A0A0R0GSZ2 View 3D Structure Click here
A0A0R0H6I8 View 3D Structure Click here
A0A0R0IHK4 View 3D Structure Click here
A0A0R0JCA6 View 3D Structure Click here
A0A0R0K9Y8 View 3D Structure Click here
A0A0R0KQP4 View 3D Structure Click here
A0A0R4IX40 View 3D Structure Click here
A0A1D6DSS4 View 3D Structure Click here
A0A1D6EIV4 View 3D Structure Click here
A0A1D6FS95 View 3D Structure Click here
A0A1D6FSG5 View 3D Structure Click here
A0A1D6HHV6 View 3D Structure Click here
A0A1D6I6S4 View 3D Structure Click here
A0A1D6I6S4 View 3D Structure Click here
A0A1D6IB93 View 3D Structure Click here
A0A1D6IGY3 View 3D Structure Click here
A0A1D6INM5 View 3D Structure Click here
A0A1D6J274 View 3D Structure Click here
A0A1D6J4H6 View 3D Structure Click here
A0A1D6JCS3 View 3D Structure Click here
A0A1D6JIA9 View 3D Structure Click here
A0A1D6JMC0 View 3D Structure Click here
A0A1D6JUI0 View 3D Structure Click here
A0A1D6KGC7 View 3D Structure Click here
A0A1D6KH75 View 3D Structure Click here
A0A1D6KH75 View 3D Structure Click here
A0A1D6LHN0 View 3D Structure Click here
A0A1D6LT02 View 3D Structure Click here
A0A1D6LT02 View 3D Structure Click here
A0A1D6M6V3 View 3D Structure Click here
A0A1D6MV17 View 3D Structure Click here
A0A1D6MVG0 View 3D Structure Click here
A0A1D6MVG0 View 3D Structure Click here
A0A1D6MYU3 View 3D Structure Click here
A0A1D6NQ37 View 3D Structure Click here
A0A1D6NQ50 View 3D Structure Click here
A0A1D6NZM7 View 3D Structure Click here
A0A1D6P1L0 View 3D Structure Click here
A0A1D6PKS6 View 3D Structure Click here
A0A1D6QMY8 View 3D Structure Click here
A0A1D8PKY1 View 3D Structure Click here
A0A1X7YH85 View 3D Structure Click here
A0A368UJD9 View 3D Structure Click here
A1L3P4 View 3D Structure Click here
A3KPJ8 View 3D Structure Click here
A4HW40 View 3D Structure Click here
A4I0D4 View 3D Structure Click here
A6NJY1 View 3D Structure Click here
B0S734 View 3D Structure Click here
B2RXE2 View 3D Structure Click here
B2RYK8 View 3D Structure Click here
B5X0N6 View 3D Structure Click here
B6U8F1 View 3D Structure Click here
B7YZY2 View 3D Structure Click here
B7ZVJ6 View 3D Structure Click here
C0HFB6 View 3D Structure Click here
C4J1R2 View 3D Structure Click here
C7J264 View 3D Structure Click here
D3ZCI2 View 3D Structure Click here
D3ZJ86 View 3D Structure Click here
D4A3Z8 View 3D Structure Click here
D4A7H1 View 3D Structure Click here
E7FBR3 View 3D Structure Click here
F1LPN2 View 3D Structure Click here
F1Q610 View 3D Structure Click here
F1Q937 View 3D Structure Click here
F1QHS0 View 3D Structure Click here
F1QR72 View 3D Structure Click here
F1R354 View 3D Structure Click here
F1R610 View 3D Structure Click here
F2X1X4 View 3D Structure Click here
G3X939 View 3D Structure Click here
G5EBK1 View 3D Structure Click here
G5EBN7 View 3D Structure Click here
G5ED88 View 3D Structure Click here
G5EDH8 View 3D Structure Click here
G5EDU2 View 3D Structure Click here
G5EFS0 View 3D Structure Click here
H2L039 View 3D Structure Click here
H9CDQ2 View 3D Structure Click here
I1JAB3 View 3D Structure Click here
I1JH50 View 3D Structure Click here
I1JPC8 View 3D Structure Click here
I1JR80 View 3D Structure Click here
I1JRJ0 View 3D Structure Click here
I1JY13 View 3D Structure Click here
I1K501 View 3D Structure Click here
I1KBK1 View 3D Structure Click here
I1KCC4 View 3D Structure Click here
I1KL77 View 3D Structure Click here
I1KNP2 View 3D Structure Click here
I1KPS4 View 3D Structure Click here
I1KQU9 View 3D Structure Click here
I1L3J4 View 3D Structure Click here
I1L5M7 View 3D Structure Click here
I1L6M4 View 3D Structure Click here
I1L9S3 View 3D Structure Click here
I1LGB4 View 3D Structure Click here
I1LLS7 View 3D Structure Click here
I1LLT4 View 3D Structure Click here
I1LMR0 View 3D Structure Click here
I1LMW1 View 3D Structure Click here
I1LVH1 View 3D Structure Click here
I1LW58 View 3D Structure Click here
I1LYC9 View 3D Structure Click here
I1LYU2 View 3D Structure Click here
I1ME88 View 3D Structure Click here
I1MFX0 View 3D Structure Click here
I1MRD9 View 3D Structure Click here
I1MS14 View 3D Structure Click here
I1MXC4 View 3D Structure Click here
I1MY95 View 3D Structure Click here
I1MZU5 View 3D Structure Click here
I1MZU6 View 3D Structure Click here
I1NBU4 View 3D Structure Click here
I1NC48 View 3D Structure Click here
K7KC60 View 3D Structure Click here
K7KQE5 View 3D Structure Click here
K7KRT8 View 3D Structure Click here
K7L085 View 3D Structure Click here
K7LA97 View 3D Structure Click here
K7LBC1 View 3D Structure Click here
K7LDJ6 View 3D Structure Click here
K7LJ58 View 3D Structure Click here
K7M853 View 3D Structure Click here
K7MF40 View 3D Structure Click here
K7MPG8 View 3D Structure Click here
K7MPH0 View 3D Structure Click here
K7MU75 View 3D Structure Click here
K7N1I5 View 3D Structure Click here
K7TWM1 View 3D Structure Click here
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K7VBL6 View 3D Structure Click here
K7VU58 View 3D Structure Click here
L7N665 View 3D Structure Click here
O13726 View 3D Structure Click here
O14123 View 3D Structure Click here
O16452 View 3D Structure Click here
O22920 View 3D Structure Click here
O65272 View 3D Structure Click here
P03819 View 3D Structure Click here
P0CG16 View 3D Structure Click here
P19634 View 3D Structure Click here
P26431 View 3D Structure Click here
P26433 View 3D Structure Click here
P26434 View 3D Structure Click here
P32703 View 3D Structure Click here
P35449 View 3D Structure Click here
P36606 View 3D Structure Click here
P39830 View 3D Structure Click here
P40309 View 3D Structure Click here
P45522 View 3D Structure Click here
P48763 View 3D Structure Click here
P48764 View 3D Structure Click here
P76007 View 3D Structure Click here
P9WJI3 View 3D Structure Click here
Q04121 View 3D Structure Click here
Q0DIK5 View 3D Structure Click here
Q0DLA4 View 3D Structure Click here
Q0DVI9 View 3D Structure Click here
Q0IJ87 View 3D Structure Click here
Q0IZW7 View 3D Structure Click here
Q0J2X1 View 3D Structure Click here
Q14940 View 3D Structure Click here
Q1HDT2 View 3D Structure Click here
Q1HDT3 View 3D Structure Click here
Q20273 View 3D Structure Click here
Q2FVI0 View 3D Structure Click here
Q2FZQ4 View 3D Structure Click here
Q2G2E0 View 3D Structure Click here
Q2QM48 View 3D Structure Click here
Q2QYF6 View 3D Structure Click here
Q2R0E9 View 3D Structure Click here
Q2RBJ3 View 3D Structure Click here
Q3EDG3 View 3D Structure Click here
Q3YL57 View 3D Structure Click here
Q3ZAS0 View 3D Structure Click here
Q4CK89 View 3D Structure Click here
Q4D226 View 3D Structure Click here
Q4D8E9 View 3D Structure Click here
Q4DSK0 View 3D Structure Click here
Q4G0N8 View 3D Structure Click here
Q4L208 View 3D Structure Click here
Q4ZJI4 View 3D Structure Click here
Q54CP6 View 3D Structure Click here
Q54GC7 View 3D Structure Click here
Q54TB5 View 3D Structure Click here
Q552S0 View 3D Structure Click here
Q56XP4 View 3D Structure Click here
Q58671 View 3D Structure Click here
Q58916 View 3D Structure Click here
Q58P69 View 3D Structure Click here
Q58P71 View 3D Structure Click here
Q59NG8 View 3D Structure Click here
Q5BKR2 View 3D Structure Click here
Q5ICN3 View 3D Structure Click here
Q5TAH2 View 3D Structure Click here
Q5Z8T1 View 3D Structure Click here
Q60362 View 3D Structure Click here
Q61165 View 3D Structure Click here
Q68KI4 View 3D Structure Click here
Q6AI14 View 3D Structure Click here
Q6ATD0 View 3D Structure Click here
Q6ESB5 View 3D Structure Click here
Q6UJY2 View 3D Structure Click here
Q6UUW2 View 3D Structure Click here
Q6UWJ1 View 3D Structure Click here
Q6ZJ60 View 3D Structure Click here
Q75J76 View 3D Structure Click here
Q84WG1 View 3D Structure Click here
Q86UD5 View 3D Structure Click here
Q8BH01 View 3D Structure Click here
Q8BLV3 View 3D Structure Click here
Q8BUE1 View 3D Structure Click here
Q8BZ00 View 3D Structure Click here
Q8C0X2 View 3D Structure Click here
Q8GX92 View 3D Structure Click here
Q8IET0 View 3D Structure Click here
Q8IPJ4 View 3D Structure Click here
Q8IVB4 View 3D Structure Click here
Q8L709 View 3D Structure Click here
Q8R4D1 View 3D Structure Click here
Q8RWU6 View 3D Structure Click here
Q8S396 View 3D Structure Click here
Q8S397 View 3D Structure Click here
Q8T5S1 View 3D Structure Click here
Q8VYD4 View 3D Structure Click here
Q8VYR9 View 3D Structure Click here
Q92581 View 3D Structure Click here
Q96T83 View 3D Structure Click here
Q99271 View 3D Structure Click here
Q9FFB7 View 3D Structure Click here
Q9FFB8 View 3D Structure Click here
Q9FFR9 View 3D Structure Click here
Q9FGH6 View 3D Structure Click here
Q9FYB9 View 3D Structure Click here
Q9FYC0 View 3D Structure Click here
Q9FYC1 View 3D Structure Click here
Q9LKW9 View 3D Structure Click here
Q9LMJ1 View 3D Structure Click here
Q9LUN4 View 3D Structure Click here
Q9M008 View 3D Structure Click here
Q9M0Z3 View 3D Structure Click here
Q9M353 View 3D Structure Click here
Q9P7I1 View 3D Structure Click here
Q9SA37 View 3D Structure Click here
Q9SAK8 View 3D Structure Click here
Q9SIT5 View 3D Structure Click here
Q9SKA9 View 3D Structure Click here
Q9SUQ7 View 3D Structure Click here
Q9SXJ8 View 3D Structure Click here
Q9UBY0 View 3D Structure Click here
Q9VM74 View 3D Structure Click here
Q9VPJ1 View 3D Structure Click here
Q9XU88 View 3D Structure Click here
Q9Y2E8 View 3D Structure Click here
Q9Z0X2 View 3D Structure Click here
Q9ZTZ7 View 3D Structure Click here
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