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Protein

Sodium/hydrogen exchanger 9B2

Gene

SLC9B2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

    EuPathDBiHostDB:ENSG00000164038.14
    HGNCiHGNC:25143 SLC9B2
    MIMi611789 gene
    neXtProtiNX_Q86UD5

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Cilium, Cytoplasmic vesicle, Endosome, Flagellum, 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

    EPDiQ86UD5
    MaxQBiQ86UD5
    PaxDbiQ86UD5
    PeptideAtlasiQ86UD5
    PRIDEiQ86UD5
    ProteomicsDBi69803
    69804 [Q86UD5-2]

    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 Expressed in 152 organ(s), highest expression level in tibia
    CleanExiHS_NHEDC2
    ExpressionAtlasiQ86UD5 baseline and differential
    GenevisibleiQ86UD5 HS

    Organism-specific databases

    HPAiHPA047008

    Interactioni

    Subunit structurei

    Homodimer (PubMed:28071645).1 Publication

    GO - Molecular functioni

    Protein-protein interaction databases

    IntActiQ86UD5, 4 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

    Gene3Di1.20.1530.20, 1 hit
    InterProiView protein in InterPro
    IPR006153 Cation/H_exchanger
    IPR038770 Na+/solute_symporter_sf
    IPR037072 SLC9B2
    PANTHERiPTHR31102:SF14 PTHR31102:SF14, 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

    This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    B7Z676B7Z676_HUMAN
    Sodium/hydrogen exchanger 9B2
    SLC9B2
    417Annotation score:
    E9PE63E9PE63_HUMAN
    Sodium/hydrogen exchanger 9B2
    SLC9B2
    480Annotation score:
    A0A0C4DGB3A0A0C4DGB3_HUMAN
    Sodium/hydrogen exchanger 9B2
    SLC9B2
    354Annotation score:
    D6RGJ7D6RGJ7_HUMAN
    Sodium/hydrogen exchanger 9B2
    SLC9B2
    143Annotation score:
    D6R9P2D6R9P2_HUMAN
    Sodium/hydrogen exchanger 9B2
    SLC9B2
    112Annotation score:

    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

    Cross-referencesi

    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

    3D structure databases

    ProteinModelPortaliQ86UD5
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    IntActiQ86UD5, 4 interactors
    STRINGi9606.ENSP00000354574

    Protein family/group databases

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

    PTM databases

    iPTMnetiQ86UD5
    PhosphoSitePlusiQ86UD5

    Polymorphism and mutation databases

    BioMutaiSLC9B2
    DMDMi121944426

    Proteomic databases

    EPDiQ86UD5
    MaxQBiQ86UD5
    PaxDbiQ86UD5
    PeptideAtlasiQ86UD5
    PRIDEiQ86UD5
    ProteomicsDBi69803
    69804 [Q86UD5-2]

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi133308
    DisGeNETi133308
    EuPathDBiHostDB:ENSG00000164038.14
    GeneCardsiSLC9B2
    HGNCiHGNC:25143 SLC9B2
    HPAiHPA047008
    MIMi611789 gene
    neXtProtiNX_Q86UD5
    OpenTargetsiENSG00000164038
    PharmGKBiPA162397515
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

    ReactomeiR-HSA-2672351 Stimuli-sensing channels

    Miscellaneous databases

    ChiTaRSiSLC9B2 human
    GenomeRNAii133308
    PROiPR:Q86UD5
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000164038 Expressed in 152 organ(s), highest expression level in tibia
    CleanExiHS_NHEDC2
    ExpressionAtlasiQ86UD5 baseline and differential
    GenevisibleiQ86UD5 HS

    Family and domain databases

    Gene3Di1.20.1530.20, 1 hit
    InterProiView protein in InterPro
    IPR006153 Cation/H_exchanger
    IPR038770 Na+/solute_symporter_sf
    IPR037072 SLC9B2
    PANTHERiPTHR31102:SF14 PTHR31102:SF14, 1 hit
    PfamiView protein in Pfam
    PF00999 Na_H_Exchanger, 1 hit
    ProtoNetiSearch...

    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: September 12, 2018
    This is version 126 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. SIMILARITY comments
      Index of protein domains and families
    2. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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