Q86UD5 · SL9B2_HUMAN

  • Protein
    Sodium/hydrogen exchanger 9B2
  • Gene
    SLC9B2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Electroneutral Na+ Li+/H+ antiporter that extrudes Na+ or Li+ in exchange for external protons across the membrane (PubMed:18000046, PubMed:18508966, PubMed:22948142, PubMed:28154142, PubMed:36177733).
Uses the proton gradient/membrane potential to extrude sodium (PubMed:22948142).
Contributes to the regulation of intracellular pH and sodium homeostasis (By similarity).
Also able to mediate Na+/Li+ antiporter activity in kidney (PubMed:22948142).
May play a physiological role in renal tubular function and blood pressure homeostasis (By similarity).
Plays an important role for insulin secretion and clathrin-mediated endocytosis in beta-cells (By similarity).
Involved in sperm motility and fertility (By similarity).
It is controversial whether SLC9B2 plays a role in osteoclast differentiation or not (By similarity).

Miscellaneous

The subcellular localization of SLC9B2 remains controversial. Was initially thought to partially localize to mitochondria (By similarity).
However SLC9B2 does not seem to contain a mitochondrial targeting sequence. It was later established that its localizes predominantly in plasma membrane or intracellularly to endosomes and lysosomes (By similarity).
In another recent study, endogenous SLC9B2 in the distal tubular cell line mpkDCT4 is detected in recycling endosomes but absent in plasma membrane (By similarity).

Catalytic activity

Activity regulation

Allosterically inhibited by the N-terminal domain (PubMed:36177733).
Inhibited by phloretin (PubMed:18000046, PubMed:36177733).

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
33 mMNa+
67 mMLi+

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site244Na+ (UniProtKB | ChEBI)
Binding site275Na+ (UniProtKB | ChEBI)
Binding site278Na+ (UniProtKB | ChEBI)
Binding site279Na+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Cellular Componentmitochondrial inner membrane
Cellular Componentmitochondrial membrane
Cellular Componentplasma membrane
Cellular Componentrecycling endosome
Cellular Componentrecycling endosome membrane
Cellular Componentsperm principal piece
Cellular Componentsynaptic vesicle membrane
Molecular Functionidentical protein binding
Molecular Functionlithium:proton antiporter activity
Molecular Functionsodium:proton antiporter activity
Biological Processclathrin-dependent endocytosis
Biological Processflagellated sperm motility
Biological Processinorganic cation transmembrane transport
Biological Processlithium ion transport
Biological Processmonoatomic ion transmembrane transport
Biological Processpositive regulation of osteoclast development
Biological Processregulation of insulin secretion involved in cellular response to glucose stimulus
Biological Processsodium ion homeostasis
Biological Processsodium ion transport

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Sodium/hydrogen exchanger 9B2
  • Alternative names
    • Na(+)/H(+) exchanger NHA2
    • Na(+)/H(+) exchanger-like domain-containing protein 2 (NHE domain-containing protein 2)
    • Sodium/hydrogen exchanger-like domain-containing protein 2
    • Solute carrier family 9 subfamily B member 2

Gene names

    • Name
      SLC9B2
    • Synonyms
      NHA2, NHEDC2

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q86UD5
  • Secondary accessions
    • B5ME52
    • Q6ZMD8
    • Q96D95

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein
Mitochondrion membrane
; Multi-pass membrane protein
Endosome membrane
; Multi-pass membrane protein
Recycling endosome membrane
; Multi-pass membrane protein
Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane
; Multi-pass membrane protein
Cell projection, cilium, flagellum membrane
; Multi-pass membrane protein
Basolateral cell membrane
; Multi-pass membrane protein
Apical cell membrane
; Multi-pass membrane protein
Note: Strong colocalization with LAMP1 and TCIRG1 in osteoclasts. In beta-cells colocalizes with RAB4A and SYP. Localizes to the basolateral membrane of polarized osteoclasts.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-86Cytoplasmic
Transmembrane87-104Helical; Name=1
Topological domain105-113Extracellular
Transmembrane114-133Helical; Name=2
Topological domain134-144Cytoplasmic
Transmembrane145-161Helical; Name=3
Topological domain162-171Extracellular
Transmembrane172-189Helical; Name=4
Topological domain190-200Cytoplasmic
Transmembrane201-227Helical; Name=5
Topological domain228-233Extracellular
Transmembrane234-242Helical; Name=6
Topological domain243-270Cytoplasmic
Transmembrane271-290Helical; Name=7
Topological domain291-300Extracellular
Transmembrane301-324Helical; Name=8
Topological domain325-339Cytoplasmic
Transmembrane340-357Helical; Name=9
Topological domain358-361Extracellular
Transmembrane362-373Helical; Name=10
Topological domain374-390Cytoplasmic
Transmembrane391-411Helical; Name=11
Topological domain412-417Extracellular
Transmembrane418-440Helical; Name=12
Topological domain441-461Cytoplasmic
Transmembrane462-473Helical; Name=13
Topological domain474-486Extracellular
Transmembrane487-509Helical; Name=14
Topological domain510-537Cytoplasmic

Keywords

Disease & Variants

Features

Showing features for mutagenesis, natural variant.

TypeIDPosition(s)Description
Mutagenesis47Decreases Na+ Li+/H+ antiporter activity.
Mutagenesis56Decreases Na+ Li+/H+ antiporter activity.
Mutagenesis57Does not affect Na+ Li+/H+ antiporter activity; when associated with A-58.
Mutagenesis57Decreases Na+ Li+/H+ antiporter activity; when associated with K-58.
Mutagenesis58Does not affect tNa+ Li+/H+ antiporter activity; when associated with A-57.
Mutagenesis58Decreases Na+ Li+/H+ antiporter activity; when associated with K-57.
Natural variantVAR_042751159in dbSNP:rs7672710
Natural variantVAR_042752161in dbSNP:rs7672707
Mutagenesis215Abolishes Na+ Li+/H+ antiporter activity. Shifts the specificity of the transporter from Na+ to Li+; when associated with E-432. Decreases plasma membrane localization. Partially retained in the ER; when associated with E-432.
Mutagenesis238Abolishes Na+ Li+/H+ antiporter activity. Changes subcellular localization. Retained in the ER.
Mutagenesis240Does not affect plasma membrane localization. Change in the substrate specificity with a preference for Li+ over Na+.
Mutagenesis246Does not affect plasma membrane localization. Less sensitive to phloretin inhibition.
Mutagenesis246Does not affect plasma membrane localization. Abolishes antiporter activity. Less sensitive to phloretin inhibition.
Mutagenesis246Does not affect plasma membrane localization. Less sensitive to phloretin inhibition.
Mutagenesis246Does not affect plasma membrane localization. Less sensitive to phloretin inhibition.
Mutagenesis278Abolishes Na+ Li+/H+ antiporter activity. Does not affect plasma membrane localization.
Mutagenesis278-279Loss of ion transport activity; Does not rescue insulin secretion defect induced by knockdown of SLC9B2 in Min6 cells.
Natural variantVAR_042753357in dbSNP:rs2276976
Mutagenesis382Does not affect plasma membrane localization. Decreases the substrate specificity for Li+.
Mutagenesis406Does not affect plasma membrane localization. Decreases Na+ Li+/H+ antiporter activity.
Mutagenesis432Abolishes Na+ Li+/H+ antiporter activity. Shifts the specificity from Na+ to Li+; when associated with R-215. Decreases plasma membrane localization; when associated with R-215. Partially retained in the ER; when associated with R-215.
Mutagenesis432Loss of ion transport activity.
Mutagenesis432Does not affect plasma membrane localization. Decreases the substrate specificity for Li+.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 689 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
ChainPRO_00003312701-537UniProtSodium/hydrogen exchanger 9B2
Modified residue49UniProtPhosphoserine
Modified residue (large scale data)49PRIDEPhosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Widely expressed (PubMed:18508966).
High levels detected in the distal tubules of the kidney nephron (PubMed:18508966).
Detected in red blood cells (at protein level) (PubMed:18000046, PubMed:18508966).

Gene expression databases

Organism-specific databases

Interaction

Subunit

Homodimer (PubMed:28071645).
Dimerization is essential for SLC9B2 activity (By similarity).
Lipids seem to play a role in the stabilization of the dimerization subdomain (By similarity).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q86UD5PGRMC2 O151733EBI-9916342, EBI-1050125

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, compositional bias.

TypeIDPosition(s)Description
Region1-28Disordered
Compositional bias13-28Polar residues

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

Q86UD5-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    537
  • Mass (Da)
    57,564
  • Last updated
    2005-08-30 v2
  • Checksum
    85A8BDA60ABE2587
MGDEDKRITYEDSEPSTGMNYTPSMHQEAQEETVMKLKGIDANEPTEGSILLKSSEKKLQETPTEANHVQRLRQMLACPPHGLLDRVITNVTIIVLLWAVVWSITGSECLPGGNLFGIIILFYCAIIGGKLLGLIKLPTLPPLPSLLGMLLAGFLIRNIPVINDNVQIKHKWSSSLRSIALSIILVRAGLGLDSKALKKLKGVCVRLSMGPCIVEACTSALLAHYLLGLPWQWGFILGFVLGAVSPAVVVPSMLLLQGGGYGVEKGVPTLLMAAGSFDDILAITGFNTCLGIAFSTGSTVFNVLRGVLEVVIGVATGSVLGFFIQYFPSRDQDKLVCKRTFLVLGLSVLAVFSSVHFGFPGSGGLCTLVMAFLAGMGWTSEKAEVEKIIAVAWDIFQPLLFGLIGAEVSIASLRPETVGLCVATVGIAVLIRILTTFLMVCFAGFNLKEKIFISFAWLPKATVQAAIGSVALDTARSHGEKQLEDYGMDVLTVAFLSILITAPIGSLLIGLLGPRLLQKVEHQNKDEEVQGETSVQV

Q86UD5-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 420-502: LCVATVGIAVLIRILTTFLMVCFAGFNLKEKIFISFAWLPKATVQAAIGSVALDTARSHGEKQLEDYGMDVLTVAFLSILITA → SADSITGNFGTERPKLLGPPSTQLRFHFFHIQLST
    • 503-537: Missing

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
D6RGJ7D6RGJ7_HUMANSLC9B2143
D6R9P2D6R9P2_HUMANSLC9B2112
B7Z676B7Z676_HUMANSLC9B2417
E9PE63E9PE63_HUMANSLC9B2480
A0A0C4DGB3A0A0C4DGB3_HUMANSLC9B2354

Features

Showing features for compositional bias, alternative sequence.

TypeIDPosition(s)Description
Compositional bias13-28Polar residues
Alternative sequenceVSP_033152420-502in isoform 2
Alternative sequenceVSP_033153503-537in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AK172823
EMBL· GenBank· DDBJ
BAD18790.1
EMBL· GenBank· DDBJ
mRNA
AC097485
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471057
EMBL· GenBank· DDBJ
EAX06159.1
EMBL· GenBank· DDBJ
Genomic DNA
BC009732
EMBL· GenBank· DDBJ
AAH09732.1
EMBL· GenBank· DDBJ
mRNA
BC047447
EMBL· GenBank· DDBJ
AAH47447.2
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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