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Protein

Sodium/hydrogen exchanger 9B2

Gene

SLC9B2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Na+/H+ antiporter that extrudes Na+ or Li+ in exchange for external protons across the membrane (PubMed:18000046, PubMed:28154142, PubMed:22948142, PubMed:18508966). Contributes to the regulation of intracellular pH, sodium homeostasis, and cell volume. 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).By similarity4 Publications

Miscellaneous

Inhibited by phloretin but not by the classical SLC9A-inhibitor amiloride (PubMed:18000046).1 Publication

Kineticsi

  1. KM=33 mM for for Na+1 Publication
  2. KM=67 mM for for Li+1 Publication

    pH dependencei

    Optimum pH is 8.5.1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei278Important for cation transport1 Publication1
    Sitei279Important for cation transport1 Publication1

    GO - Molecular functioni

    • identical protein binding Source: UniProtKB
    • lithium:proton antiporter activity Source: UniProtKB
    • monovalent cation:proton antiporter activity Source: Reactome
    • sodium:proton antiporter activity Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Biological processAntiport, Hydrogen ion transport, Ion transport, Sodium transport, Transport
    LigandSodium

    Enzyme and pathway databases

    ReactomeiR-HSA-2672351. Stimuli-sensing channels.

    Protein family/group databases

    TCDBi2.A.36.2.2. the monovalent cation:proton antiporter-1 (cpa1) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sodium/hydrogen exchanger 9B2
    Alternative name(s):
    Na(+)/H(+) exchanger NHA2
    Na(+)/H(+) exchanger-like domain-containing protein 2
    Short name:
    NHE domain-containing protein 2
    Sodium/hydrogen exchanger-like domain-containing protein 2
    Solute carrier family 9 subfamily B member 2
    Gene namesi
    Name:SLC9B2
    Synonyms:NHA2, NHEDC2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:25143. SLC9B2.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transmembranei87 – 107HelicalSequence analysisAdd BLAST21
    Transmembranei115 – 135HelicalSequence analysisAdd BLAST21
    Transmembranei136 – 156HelicalSequence analysisAdd BLAST21
    Transmembranei209 – 229HelicalSequence analysisAdd BLAST21
    Transmembranei235 – 255HelicalSequence analysisAdd BLAST21
    Transmembranei266 – 286HelicalSequence analysisAdd BLAST21
    Transmembranei307 – 327HelicalSequence analysisAdd BLAST21
    Transmembranei341 – 361HelicalSequence analysisAdd BLAST21
    Transmembranei363 – 383HelicalSequence analysisAdd BLAST21
    Transmembranei388 – 408HelicalSequence analysisAdd BLAST21
    Transmembranei425 – 445HelicalSequence analysisAdd BLAST21
    Transmembranei493 – 513HelicalSequence analysisAdd BLAST21

    GO - Cellular componenti

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Cytoplasmic vesicle, Endosome, Membrane, Mitochondrion, Synapse

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi278 – 279DD → CC: Loss of ion transport activity; Does not rescue insulin secretion defect induced by knockdown of SLC9B2 in Min6 cells. 2 Publications2
    Mutagenesisi432R → K or H: Loss of ion transport activity;. 1 Publication1

    Organism-specific databases

    DisGeNETi133308.
    OpenTargetsiENSG00000164038.
    PharmGKBiPA162397515.

    Polymorphism and mutation databases

    BioMutaiSLC9B2.
    DMDMi121944426.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00003312701 – 537Sodium/hydrogen exchanger 9B2Add BLAST537

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei49PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ86UD5.
    PaxDbiQ86UD5.
    PeptideAtlasiQ86UD5.
    PRIDEiQ86UD5.

    PTM databases

    iPTMnetiQ86UD5.
    PhosphoSitePlusiQ86UD5.

    Expressioni

    Tissue specificityi

    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).2 Publications

    Gene expression databases

    BgeeiENSG00000164038.
    CleanExiHS_NHEDC2.
    ExpressionAtlasiQ86UD5. baseline and differential.
    GenevisibleiQ86UD5. HS.

    Organism-specific databases

    HPAiHPA047008.

    Interactioni

    Subunit structurei

    Homodimer (PubMed:28071645).1 Publication

    GO - Molecular functioni

    • identical protein binding Source: UniProtKB

    Protein-protein interaction databases

    IntActiQ86UD5. 3 interactors.
    STRINGi9606.ENSP00000354574.

    Structurei

    3D structure databases

    ProteinModelPortaliQ86UD5.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3826. Eukaryota.
    COG0025. LUCA.
    GeneTreeiENSGT00390000013285.
    HOGENOMiHOG000060325.
    HOVERGENiHBG108184.
    InParanoidiQ86UD5.
    OMAiKKVGRPA.
    OrthoDBiEOG091G06PH.
    PhylomeDBiQ86UD5.
    TreeFamiTF319087.

    Family and domain databases

    InterProiView protein in InterPro
    IPR006153. Cation/H_exchanger.
    IPR030187. NHA.
    PANTHERiPTHR31102:SF9. PTHR31102:SF9. 1 hit.
    PfamiView protein in Pfam
    PF00999. Na_H_Exchanger. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q86UD5-1) [UniParc]FASTAAdd to basket

    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.

    « Hide

            10         20         30         40         50
    MGDEDKRITY EDSEPSTGMN YTPSMHQEAQ EETVMKLKGI DANEPTEGSI
    60 70 80 90 100
    LLKSSEKKLQ ETPTEANHVQ RLRQMLACPP HGLLDRVITN VTIIVLLWAV
    110 120 130 140 150
    VWSITGSECL PGGNLFGIII LFYCAIIGGK LLGLIKLPTL PPLPSLLGML
    160 170 180 190 200
    LAGFLIRNIP VINDNVQIKH KWSSSLRSIA LSIILVRAGL GLDSKALKKL
    210 220 230 240 250
    KGVCVRLSMG PCIVEACTSA LLAHYLLGLP WQWGFILGFV LGAVSPAVVV
    260 270 280 290 300
    PSMLLLQGGG YGVEKGVPTL LMAAGSFDDI LAITGFNTCL GIAFSTGSTV
    310 320 330 340 350
    FNVLRGVLEV VIGVATGSVL GFFIQYFPSR DQDKLVCKRT FLVLGLSVLA
    360 370 380 390 400
    VFSSVHFGFP GSGGLCTLVM AFLAGMGWTS EKAEVEKIIA VAWDIFQPLL
    410 420 430 440 450
    FGLIGAEVSI ASLRPETVGL CVATVGIAVL IRILTTFLMV CFAGFNLKEK
    460 470 480 490 500
    IFISFAWLPK ATVQAAIGSV ALDTARSHGE KQLEDYGMDV LTVAFLSILI
    510 520 530
    TAPIGSLLIG LLGPRLLQKV EHQNKDEEVQ GETSVQV
    Length:537
    Mass (Da):57,564
    Last modified:August 30, 2005 - v2
    Checksum:i85A8BDA60ABE2587
    GO
    Isoform 2 (identifier: Q86UD5-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         420-502: LCVATVGIAV...VAFLSILITA → SADSITGNFGTERPKLLGPPSTQLRFHFFHIQLST
         503-537: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:454
    Mass (Da):48,710
    Checksum:i75C1A26C290D3908
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_042751159I → T. Corresponds to variant dbSNP:rs7672710Ensembl.1
    Natural variantiVAR_042752161V → A. Corresponds to variant dbSNP:rs7672707Ensembl.1
    Natural variantiVAR_042753357F → C. Corresponds to variant dbSNP:rs2276976Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_033152420 – 502LCVAT…ILITA → SADSITGNFGTERPKLLGPP STQLRFHFFHIQLST in isoform 2. 1 PublicationAdd BLAST83
    Alternative sequenceiVSP_033153503 – 537Missing in isoform 2. 1 PublicationAdd BLAST35

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AK172823 mRNA. Translation: BAD18790.1.
    AC097485 Genomic DNA. No translation available.
    CH471057 Genomic DNA. Translation: EAX06159.1.
    BC009732 mRNA. Translation: AAH09732.1.
    BC047447 mRNA. Translation: AAH47447.2.
    CCDSiCCDS3662.1. [Q86UD5-1]
    RefSeqiNP_001287685.1. NM_001300756.1.
    NP_849155.2. NM_178833.5. [Q86UD5-1]
    XP_006714148.1. XM_006714085.2. [Q86UD5-1]
    UniGeneiHs.546482.

    Genome annotation databases

    EnsembliENST00000362026; ENSP00000354574; ENSG00000164038. [Q86UD5-1]
    ENST00000394785; ENSP00000378265; ENSG00000164038. [Q86UD5-1]
    GeneIDi133308.
    KEGGihsa:133308.
    UCSCiuc003hwx.5. human. [Q86UD5-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiSL9B2_HUMAN
    AccessioniPrimary (citable) accession number: Q86UD5
    Secondary accession number(s): B5ME52, Q6ZMD8, Q96D95
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 29, 2008
    Last sequence update: August 30, 2005
    Last modified: August 30, 2017
    This is version 119 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families