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Protein

Sodium/hydrogen exchanger 1

Gene

SLC9A1

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

Functioni

Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction.3 Publications

pH dependencei

Fully active at acidic pHs, the antiporter is virtually turned off at neutral pH.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei161 – 1611Channel pore-liningCurated
Sitei370 – 3701Not glycosylated

GO - Molecular functioni

  1. calcium-dependent protein binding Source: UniProtKB
  2. phosphatidylinositol-4,5-bisphosphate binding Source: BHF-UCL
  3. protein binding, bridging Source: BHF-UCL
  4. protein complex scaffold Source: BHF-UCL
  5. protein phosphatase 2B binding Source: BHF-UCL
  6. sodium:proton antiporter activity Source: UniProtKB
  7. sodium:proton antiporter activity involved in regulation of cardiac muscle cell membrane potential Source: BHF-UCL
  8. solute:proton antiporter activity Source: UniProtKB

GO - Biological processi

  1. carbohydrate metabolic process Source: Reactome
  2. cardiac muscle cell contraction Source: Ensembl
  3. cardiac muscle cell differentiation Source: Ensembl
  4. cell growth Source: Ensembl
  5. cell migration Source: BHF-UCL
  6. cellular response to acidic pH Source: UniProtKB
  7. cellular response to antibiotic Source: Ensembl
  8. cellular response to electrical stimulus Source: Ensembl
  9. cellular response to epinephrine stimulus Source: BHF-UCL
  10. cellular response to hypoxia Source: Ensembl
  11. cellular response to insulin stimulus Source: Ensembl
  12. cellular response to mechanical stimulus Source: BHF-UCL
  13. cellular sodium ion homeostasis Source: BHF-UCL
  14. glycosaminoglycan metabolic process Source: Reactome
  15. hyaluronan catabolic process Source: Reactome
  16. hyaluronan metabolic process Source: Reactome
  17. hydrogen ion transmembrane transport Source: BHF-UCL
  18. ion transport Source: Reactome
  19. maintenance of cell polarity Source: BHF-UCL
  20. negative regulation of apoptotic process Source: Ensembl
  21. neuron death Source: Ensembl
  22. positive regulation of action potential Source: Ensembl
  23. positive regulation of calcineurin-NFAT signaling cascade Source: BHF-UCL
  24. positive regulation of calcium:sodium antiporter activity Source: BHF-UCL
  25. positive regulation of cardiac muscle hypertrophy Source: BHF-UCL
  26. positive regulation of cell growth Source: Ensembl
  27. positive regulation of mitochondrial membrane permeability Source: Ensembl
  28. positive regulation of NFAT protein import into nucleus Source: BHF-UCL
  29. positive regulation of the force of heart contraction Source: BHF-UCL
  30. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  31. protein oligomerization Source: UniProtKB
  32. regulation of cardiac muscle cell membrane potential Source: BHF-UCL
  33. regulation of cardiac muscle contraction by calcium ion signaling Source: BHF-UCL
  34. regulation of focal adhesion assembly Source: BHF-UCL
  35. regulation of intracellular pH Source: UniProtKB
  36. regulation of pH Source: UniProtKB
  37. regulation of sensory perception of pain Source: Ensembl
  38. regulation of stress fiber assembly Source: BHF-UCL
  39. regulation of the force of heart contraction by cardiac conduction Source: BHF-UCL
  40. response to acidic pH Source: UniProtKB
  41. response to drug Source: Ensembl
  42. response to muscle stretch Source: BHF-UCL
  43. small molecule metabolic process Source: Reactome
  44. sodium ion export Source: UniProtKB
  45. sodium ion import across plasma membrane Source: BHF-UCL
  46. transmembrane transport Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Antiport, Ion transport, Sodium transport, Transport

Keywords - Ligandi

Calmodulin-binding, Sodium

Enzyme and pathway databases

ReactomeiREACT_120996. Hyaluronan uptake and degradation.
REACT_19314. Sodium/Proton exchangers.
SignaLinkiP19634.

Protein family/group databases

TCDBi2.A.36.1.13. the monovalent cation:proton antiporter-1 (cpa1) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/hydrogen exchanger 1
Alternative name(s):
APNH
Na(+)/H(+) antiporter, amiloride-sensitive
Na(+)/H(+) exchanger 1
Short name:
NHE-1
Solute carrier family 9 member 1
Gene namesi
Name:SLC9A1
Synonyms:APNH1, NHE1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:11071. SLC9A1.

Subcellular locationi

Membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity. Cell membrane; Multi-pass membrane protein
Note: Colocalizes with CHP1 at the reticulum endoplasmic (By similarity). Colocalizes with CHP1 and CHP2 at the plasma membrane.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1212CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei13 – 3321Helical; Name=M1Sequence AnalysisAdd
BLAST
Topological domaini34 – 10572ExtracellularSequence AnalysisAdd
BLAST
Transmembranei106 – 12722Helical; Name=M2Sequence AnalysisAdd
BLAST
Topological domaini128 – 1292CytoplasmicSequence Analysis
Transmembranei130 – 14920Helical; Name=M3Sequence AnalysisAdd
BLAST
Topological domaini150 – 1545ExtracellularSequence Analysis
Transmembranei155 – 17420Helical; Name=M4Sequence AnalysisAdd
BLAST
Topological domaini175 – 19117CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei192 – 21120Helical; Name=M5Sequence AnalysisAdd
BLAST
Topological domaini212 – 22716ExtracellularSequence AnalysisAdd
BLAST
Transmembranei228 – 24720Helical; Name=M6Sequence AnalysisAdd
BLAST
Topological domaini248 – 2569CytoplasmicSequence Analysis
Transmembranei257 – 27620Helical; Name=M7Sequence AnalysisAdd
BLAST
Topological domaini277 – 29418ExtracellularSequence AnalysisAdd
BLAST
Transmembranei295 – 31521Helical; Name=M8Sequence AnalysisAdd
BLAST
Topological domaini316 – 33823CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei339 – 35820Helical; Name=M9Sequence AnalysisAdd
BLAST
Topological domaini359 – 38123ExtracellularSequence AnalysisAdd
BLAST
Intramembranei382 – 40221Name=H10By similarityAdd
BLAST
Topological domaini403 – 4108ExtracellularSequence Analysis
Transmembranei411 – 43020Helical; Name=M10Sequence AnalysisAdd
BLAST
Topological domaini431 – 44818CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei449 – 47022Helical; Name=M11Sequence AnalysisAdd
BLAST
Topological domaini471 – 4799ExtracellularSequence Analysis
Transmembranei480 – 49920Helical; Name=M12Sequence AnalysisAdd
BLAST
Topological domaini500 – 815316CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. apical plasma membrane Source: Ensembl
  2. basolateral plasma membrane Source: Ensembl
  3. cation-transporting ATPase complex Source: BHF-UCL
  4. cell surface Source: Ensembl
  5. cytoplasm Source: UniProtKB
  6. endoplasmic reticulum Source: UniProtKB
  7. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  8. extracellular vesicular exosome Source: UniProtKB
  9. focal adhesion Source: UniProtKB
  10. integral component of membrane Source: UniProtKB
  11. integral component of plasma membrane Source: BHF-UCL
  12. intercalated disc Source: Ensembl
  13. lamellipodium Source: BHF-UCL
  14. membrane raft Source: BHF-UCL
  15. mitochondrion Source: Ensembl
  16. nucleoplasm Source: HPA
  17. perinuclear region of cytoplasm Source: Ensembl
  18. plasma membrane Source: UniProtKB
  19. T-tubule Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi155 – 1551F → C: Almost complete loss of activity. 1 Publication
Mutagenesisi156 – 1561L → C: Almost complete loss of activity. 1 Publication
Mutagenesisi157 – 1571Q → C: Reduces activity. 1 Publication
Mutagenesisi158 – 1581S → C: Almost complete loss of activity. 1 Publication
Mutagenesisi159 – 1591D → C: Almost complete loss of activity. 1 Publication
Mutagenesisi160 – 1601V → C: Reduces activity. 1 Publication
Mutagenesisi161 – 1611F → C: Reduces activity. 1 Publication
Mutagenesisi162 – 1621F → C: Almost complete loss of activity. 1 Publication
Mutagenesisi163 – 1631L → C: Reduces activity. 1 Publication
Mutagenesisi164 – 1641F → C: Almost complete loss of activity. 1 Publication
Mutagenesisi165 – 1651L → C: Reduces activity. 1 Publication
Mutagenesisi166 – 1661L → C: Reduces activity. 1 Publication
Mutagenesisi167 – 1671P → A: Reduces activity. 2 Publications
Mutagenesisi167 – 1671P → C or G: Almost complete loss of activity. Reduces membrane localization. 2 Publications
Mutagenesisi168 – 1681P → A or C: Almost complete loss of activity. 2 Publications
Mutagenesisi168 – 1681P → G: Reduces activity. 2 Publications
Mutagenesisi169 – 1691I → C: Reduces activity. 1 Publication
Mutagenesisi170 – 1701I → C: Reduces activity. 1 Publication
Mutagenesisi171 – 1711L → C: Reduces activity. 1 Publication
Mutagenesisi172 – 1721D → C: Almost complete loss of activity. 1 Publication
Mutagenesisi173 – 1731A → C: Reduces activity. 1 Publication
Mutagenesisi174 – 1741G → C: Reduces activity. 1 Publication
Mutagenesisi175 – 1751Y → C: Almost complete loss of activity. 1 Publication
Mutagenesisi176 – 1761F → C: Almost complete loss of activity. 1 Publication
Mutagenesisi177 – 1771L → C: Reduces activity. 1 Publication
Mutagenesisi178 – 1781P → A: No effect.
Mutagenesisi180 – 1801R → C: Reduces activity. 1 Publication
Mutagenesisi181 – 1811Q → C: Reduces activity. 1 Publication
Mutagenesisi518 – 5181I → Q: Reduces interaction with CHP1 and the exchange activity; when associated with Q-522. 1 Publication
Mutagenesisi522 – 5221I → Q: Reduces interaction with CHP1 and the exchange activity; when associated with Q-518. 1 Publication
Mutagenesisi526 – 5316FLDHLL → QQDHQQ: Inhibits interaction with CHP1 and the exchange activity. CHPI does not localize at the cell membrane. 1 Publication
Mutagenesisi526 – 5316FLDHLL → RRDHRR: Inhibits interaction with CHP1 and the exchange activity. CHPI does not localize at the cell membrane. 1 Publication
Mutagenesisi526 – 5261F → Q: Reduces interaction with CHP1 and the exchange activity; when associated with Q-527. 1 Publication
Mutagenesisi527 – 5271L → Q: Reduces interaction with CHP1 and the exchange activity; when associated with Q-526. 1 Publication
Mutagenesisi530 – 5301L → Q: Reduces interaction with CHP1 and the exchange activity; when associated with Q-531. 1 Publication
Mutagenesisi531 – 5311L → Q: Reduces interaction with CHP1 and the exchange activity; when associated with Q-530. 1 Publication
Mutagenesisi534 – 5341I → D or K: Strongly reduced interaction with CHP2. 1 Publication
Mutagenesisi537 – 5371I → K: Strongly reduced interaction with CHP2. 1 Publication

Organism-specific databases

PharmGKBiPA35928.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 815815Sodium/hydrogen exchanger 1PRO_0000052347Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi75 – 751N-linked (GlcNAc...)1 Publication
Modified residuei599 – 5991PhosphoserineBy similarity
Modified residuei605 – 6051PhosphoserineBy similarity
Modified residuei693 – 6931PhosphoserineBy similarity
Modified residuei697 – 6971Phosphoserine1 Publication
Modified residuei703 – 7031Phosphoserine5 Publications
Modified residuei723 – 7231Phosphoserine1 Publication
Modified residuei726 – 7261Phosphoserine1 Publication
Modified residuei729 – 7291Phosphoserine1 Publication
Modified residuei785 – 7851Phosphoserine1 Publication

Post-translational modificationi

O-glycosylated.1 Publication
Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1 (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP19634.
PaxDbiP19634.
PRIDEiP19634.

PTM databases

PhosphoSiteiP19634.

Expressioni

Tissue specificityi

Kidney and intestine.

Gene expression databases

BgeeiP19634.
CleanExiHS_SLC9A1.
ExpressionAtlasiP19634. baseline and differential.
GenevestigatoriP19634.

Organism-specific databases

HPAiCAB022371.
HPA052891.

Interactioni

Subunit structurei

Oligomer (By similarity). Interacts with calmodulin and TESC. Interacts (via the juxtamembrane region of the cytoplasmic C-terminal domain) with CHP1; the interaction occurs at the plasma membrane in a calcium-dependent manner. Interacts with CHP2; the interaction occurs in a calcium-dependent manner.By similarity10 Publications

Protein-protein interaction databases

BioGridi112438. 18 interactions.
IntActiP19634. 6 interactions.
MINTiMINT-194742.
STRINGi9606.ENSP00000263980.

Structurei

Secondary structure

1
815
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi162 – 1654Combined sources
Helixi171 – 1744Combined sources
Helixi177 – 1804Combined sources
Helixi231 – 2344Combined sources
Helixi239 – 24911Combined sources
Turni252 – 2543Combined sources
Turni256 – 2583Combined sources
Helixi259 – 26911Combined sources
Turni271 – 2733Combined sources
Helixi448 – 4514Combined sources
Turni452 – 4554Combined sources
Helixi459 – 47113Combined sources
Helixi518 – 53821Combined sources
Helixi625 – 65127Combined sources
Helixi658 – 68124Combined sources
Turni682 – 6843Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1Y4ENMR-A155-180[»]
2BECX-ray2.70B503-545[»]
2E30NMR-B503-545[»]
2HTGNMR-A250-274[»]
2KBVNMR-A447-472[»]
2L0ENMR-A226-250[»]
2MDFNMR-A226-274[»]
2YGGX-ray2.23A622-689[»]
ProteinModelPortaliP19634.
SMRiP19634. Positions 155-180, 226-274, 338-365, 447-472, 503-545, 622-685.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP19634.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni516 – 53924Interaction with CHP2Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0025.
GeneTreeiENSGT00760000119074.
HOGENOMiHOG000247044.
HOVERGENiHBG052615.
InParanoidiP19634.
KOiK05742.
OMAiKPIMIST.
OrthoDBiEOG7XWPN4.
PhylomeDBiP19634.
TreeFamiTF317212.

Family and domain databases

InterProiIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR001970. Na/H_exchanger_1.
IPR004709. NaH_exchanger.
[Graphical view]
PANTHERiPTHR10110. PTHR10110. 1 hit.
PfamiPF00999. Na_H_Exchanger. 1 hit.
[Graphical view]
PRINTSiPR01084. NAHEXCHNGR.
PR01085. NAHEXCHNGR1.
TIGRFAMsiTIGR00840. b_cpa1. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P19634-1) [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
MVLRSGICGL SPHRIFPSLL VVVALVGLLP VLRSHGLQLS PTASTIRSSE
60 70 80 90 100
PPRERSIGDV TTAPPEVTPE SRPVNHSVTD HGMKPRKAFP VLGIDYTHVR
110 120 130 140 150
TPFEISLWIL LACLMKIGFH VIPTISSIVP ESCLLIVVGL LVGGLIKGVG
160 170 180 190 200
ETPPFLQSDV FFLFLLPPII LDAGYFLPLR QFTENLGTIL IFAVVGTLWN
210 220 230 240 250
AFFLGGLMYA VCLVGGEQIN NIGLLDNLLF GSIISAVDPV AVLAVFEEIH
260 270 280 290 300
INELLHILVF GESLLNDAVT VVLYHLFEEF ANYEHVGIVD IFLGFLSFFV
310 320 330 340 350
VALGGVLVGV VYGVIAAFTS RFTSHIRVIE PLFVFLYSYM AYLSAELFHL
360 370 380 390 400
SGIMALIASG VVMRPYVEAN ISHKSHTTIK YFLKMWSSVS ETLIFIFLGV
410 420 430 440 450
STVAGSHHWN WTFVISTLLF CLIARVLGVL GLTWFINKFR IVKLTPKDQF
460 470 480 490 500
IIAYGGLRGA IAFSLGYLLD KKHFPMCDLF LTAIITVIFF TVFVQGMTIR
510 520 530 540 550
PLVDLLAVKK KQETKRSINE EIHTQFLDHL LTGIEDICGH YGHHHWKDKL
560 570 580 590 600
NRFNKKYVKK CLIAGERSKE PQLIAFYHKM EMKQAIELVE SGGMGKIPSA
610 620 630 640 650
VSTVSMQNIH PKSLPSERIL PALSKDKEEE IRKILRNNLQ KTRQRLRSYN
660 670 680 690 700
RHTLVADPYE EAWNQMLLRR QKARQLEQKI NNYLTVPAHK LDSPTMSRAR
710 720 730 740 750
IGSDPLAYEP KEDLPVITID PASPQSPESV DLVNEELKGK VLGLSRDPAK
760 770 780 790 800
VAEEDEDDDG GIMMRSKETS SPGTDDVFTP APSDSPSSQR IQRCLSDPGP
810
HPEPGEGEPF FPKGQ
Length:815
Mass (Da):90,763
Last modified:November 1, 1991 - v2
Checksum:i02EC748C79DF6526
GO
Isoform 2 (identifier: P19634-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     496-554: GMTIRPLVDL...HWKDKLNRFN → VLGQGRAGPC...FWASVSSIVK
     555-815: Missing.

Note: No experimental confirmation available.

Show »
Length:555
Mass (Da):61,013
Checksum:i961A4B1AEDEA68A5
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti682 – 6821N → K.
Corresponds to variant rs35703140 [ dbSNP | Ensembl ].
VAR_050231

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei496 – 55459GMTIR…LNRFN → VLGQGRAGPCLGDPHRLFPW KERKACDLKCDSSPSSTTNL LCDLGRATPPFWASVSSIVK in isoform 2. 1 PublicationVSP_022101Add
BLAST
Alternative sequencei555 – 815261Missing in isoform 2. 1 PublicationVSP_022102Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81768 mRNA. Translation: AAB59460.1. Sequence problems.
S68616 mRNA. Translation: AAC60606.1.
AF141350 mRNA. Translation: AAF21350.1.
AF141351 mRNA. Translation: AAF21351.1.
AF141352 mRNA. Translation: AAF21352.1.
AF141353 mRNA. Translation: AAF21353.1.
AF141354 mRNA. Translation: AAF21354.1.
AF141355 mRNA. Translation: AAF21355.1.
AF141356 mRNA. Translation: AAF21356.1.
AF141357 mRNA. Translation: AAF21357.1.
AF141358 mRNA. Translation: AAF21358.1.
AF141359 mRNA. Translation: AAF21359.1.
AF146430 mRNA. Translation: AAF25592.1.
AF146431 mRNA. Translation: AAF25593.1.
AF146432 mRNA. Translation: AAF25594.1.
AF146433 mRNA. Translation: AAF25595.1.
AF146434 mRNA. Translation: AAF25596.1.
AF146435 mRNA. Translation: AAF25597.1.
AF146436 mRNA. Translation: AAF25598.1.
AF146437 mRNA. Translation: AAF25599.1.
AF146438 mRNA. Translation: AAF25600.1.
AF146439 mRNA. Translation: AAF25601.1.
AL590640, AL137860 Genomic DNA. Translation: CAH73555.1.
AL590640, AL137860 Genomic DNA. Translation: CAH73556.1.
AL137860, AL590640 Genomic DNA. Translation: CAI22089.1.
AL137860, AL590640 Genomic DNA. Translation: CAI22090.1.
CH471059 Genomic DNA. Translation: EAX07773.1.
CH471059 Genomic DNA. Translation: EAX07774.1.
BC012121 mRNA. Translation: AAH12121.1.
CCDSiCCDS295.1. [P19634-1]
PIRiI57487.
RefSeqiNP_003038.2. NM_003047.4. [P19634-1]
UniGeneiHs.469116.
Hs.91389.

Genome annotation databases

EnsembliENST00000263980; ENSP00000263980; ENSG00000090020. [P19634-1]
ENST00000374086; ENSP00000363199; ENSG00000090020. [P19634-2]
GeneIDi6548.
KEGGihsa:6548.
UCSCiuc001bnm.4. human. [P19634-1]
uc001bnn.3. human. [P19634-2]

Polymorphism databases

DMDMi127809.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81768 mRNA. Translation: AAB59460.1. Sequence problems.
S68616 mRNA. Translation: AAC60606.1.
AF141350 mRNA. Translation: AAF21350.1.
AF141351 mRNA. Translation: AAF21351.1.
AF141352 mRNA. Translation: AAF21352.1.
AF141353 mRNA. Translation: AAF21353.1.
AF141354 mRNA. Translation: AAF21354.1.
AF141355 mRNA. Translation: AAF21355.1.
AF141356 mRNA. Translation: AAF21356.1.
AF141357 mRNA. Translation: AAF21357.1.
AF141358 mRNA. Translation: AAF21358.1.
AF141359 mRNA. Translation: AAF21359.1.
AF146430 mRNA. Translation: AAF25592.1.
AF146431 mRNA. Translation: AAF25593.1.
AF146432 mRNA. Translation: AAF25594.1.
AF146433 mRNA. Translation: AAF25595.1.
AF146434 mRNA. Translation: AAF25596.1.
AF146435 mRNA. Translation: AAF25597.1.
AF146436 mRNA. Translation: AAF25598.1.
AF146437 mRNA. Translation: AAF25599.1.
AF146438 mRNA. Translation: AAF25600.1.
AF146439 mRNA. Translation: AAF25601.1.
AL590640, AL137860 Genomic DNA. Translation: CAH73555.1.
AL590640, AL137860 Genomic DNA. Translation: CAH73556.1.
AL137860, AL590640 Genomic DNA. Translation: CAI22089.1.
AL137860, AL590640 Genomic DNA. Translation: CAI22090.1.
CH471059 Genomic DNA. Translation: EAX07773.1.
CH471059 Genomic DNA. Translation: EAX07774.1.
BC012121 mRNA. Translation: AAH12121.1.
CCDSiCCDS295.1. [P19634-1]
PIRiI57487.
RefSeqiNP_003038.2. NM_003047.4. [P19634-1]
UniGeneiHs.469116.
Hs.91389.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1Y4ENMR-A155-180[»]
2BECX-ray2.70B503-545[»]
2E30NMR-B503-545[»]
2HTGNMR-A250-274[»]
2KBVNMR-A447-472[»]
2L0ENMR-A226-250[»]
2MDFNMR-A226-274[»]
2YGGX-ray2.23A622-689[»]
ProteinModelPortaliP19634.
SMRiP19634. Positions 155-180, 226-274, 338-365, 447-472, 503-545, 622-685.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112438. 18 interactions.
IntActiP19634. 6 interactions.
MINTiMINT-194742.
STRINGi9606.ENSP00000263980.

Chemistry

BindingDBiP19634.
ChEMBLiCHEMBL2781.
DrugBankiDB00594. Amiloride.

Protein family/group databases

TCDBi2.A.36.1.13. the monovalent cation:proton antiporter-1 (cpa1) family.

PTM databases

PhosphoSiteiP19634.

Polymorphism databases

DMDMi127809.

Proteomic databases

MaxQBiP19634.
PaxDbiP19634.
PRIDEiP19634.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263980; ENSP00000263980; ENSG00000090020. [P19634-1]
ENST00000374086; ENSP00000363199; ENSG00000090020. [P19634-2]
GeneIDi6548.
KEGGihsa:6548.
UCSCiuc001bnm.4. human. [P19634-1]
uc001bnn.3. human. [P19634-2]

Organism-specific databases

CTDi6548.
GeneCardsiGC01M027425.
HGNCiHGNC:11071. SLC9A1.
HPAiCAB022371.
HPA052891.
MIMi107310. gene.
neXtProtiNX_P19634.
PharmGKBiPA35928.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0025.
GeneTreeiENSGT00760000119074.
HOGENOMiHOG000247044.
HOVERGENiHBG052615.
InParanoidiP19634.
KOiK05742.
OMAiKPIMIST.
OrthoDBiEOG7XWPN4.
PhylomeDBiP19634.
TreeFamiTF317212.

Enzyme and pathway databases

ReactomeiREACT_120996. Hyaluronan uptake and degradation.
REACT_19314. Sodium/Proton exchangers.
SignaLinkiP19634.

Miscellaneous databases

ChiTaRSiSLC9A1. human.
EvolutionaryTraceiP19634.
GeneWikiiSodium%E2%80%93hydrogen_antiporter_1.
GenomeRNAii6548.
NextBioi25485.
PROiP19634.
SOURCEiSearch...

Gene expression databases

BgeeiP19634.
CleanExiHS_SLC9A1.
ExpressionAtlasiP19634. baseline and differential.
GenevestigatoriP19634.

Family and domain databases

InterProiIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR001970. Na/H_exchanger_1.
IPR004709. NaH_exchanger.
[Graphical view]
PANTHERiPTHR10110. PTHR10110. 1 hit.
PfamiPF00999. Na_H_Exchanger. 1 hit.
[Graphical view]
PRINTSiPR01084. NAHEXCHNGR.
PR01085. NAHEXCHNGR1.
TIGRFAMsiTIGR00840. b_cpa1. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning, primary structure, and expression of the human growth factor-activatable Na+/H+ antiporter."
    Sardet C., Franchi A., Pouyssegur J.
    Cell 56:271-280(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Kidney.
  2. "Growth factors induce phosphorylation of the Na+/H+ antiporter, glycoprotein of 110 kD."
    Sardet C., Counillon L., Franchi A., Pouyssegur J.
    Science 247:723-726(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Kidney.
  3. "Molecular cloning and expression of a cDNA encoding the rabbit ileal villus cell basolateral membrane Na+/H+ exchanger."
    Tse C.-M., Ma A.I., Yang V.W., Watson A.J.M., Levine S., Montrose M.H., Potter J., Sardet C., Pouyssegur J., Donowitz M.
    EMBO J. 10:1957-1967(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: SEQUENCE REVISION.
  4. "Cloning and analysis of the human myocardial Na+/H+ exchanger."
    Fliegel L., Dyck J.R., Wang H., Fong C., Haworth R.S.
    Mol. Cell. Biochem. 125:137-143(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Heart.
  5. "Silent polymorphisms within the coding region of human sodium/hydrogen exchanger isoform-1 cDNA in peripheral blood mononuclear cells of leukemia patients: a comparison with healthy controls."
    Garden O.A., Musk P., Worthington-White D.A., Dewey M.J., Rich I.N.
    Cancer Genet. Cytogenet. 120:37-43(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  6. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Placenta.
  9. "The Na+/H+ exchanger NHE-1 possesses N- and O-linked glycosylation restricted to the first N-terminal extracellular domain."
    Counillon L., Pouyssegur J., Reithmeier R.A.
    Biochemistry 33:10463-10469(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT ASN-75, O-LINKED GLYCOSYLATION.
  10. "Coimmunoprecipitation of a 24-kDa protein with NHE1, the ubiquitous isoform of the Na+/H+ exchanger."
    Goss G., Orlowski J., Grinstein S.
    Am. J. Physiol. 270:C1493-C1502(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CHP1.
  11. "A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange."
    Lin X., Barber D.L.
    Proc. Natl. Acad. Sci. U.S.A. 93:12631-12636(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PH REGULATION, INTERACTION WITH CHP1.
  12. "Topological analysis of NHE1, the ubiquitous Na+/H+ exchanger using chymotryptic cleavage."
    Shrode L.D., Gan B.S., D'Souza S.J., Orlowski J., Grinstein S.
    Am. J. Physiol. 275:C431-C439(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY.
  13. "A novel topology model of the human Na(+)/H(+) exchanger isoform 1."
    Wakabayashi S., Pang T., Su X., Shigekawa M.
    J. Biol. Chem. 275:7942-7949(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOPOLOGY, MUTAGENESIS OF ARG-180 AND GLN-181.
  14. "Human homolog of mouse tescalcin associates with Na(+)/H(+) exchanger type-1."
    Mailaender J., Mueller-Esterl W., Dedio J.
    FEBS Lett. 507:331-335(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TESC, SUBCELLULAR LOCATION.
  15. "Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers."
    Pang T., Su X., Wakabayashi S., Shigekawa M.
    J. Biol. Chem. 276:17367-17372(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CHP1, MUTAGENESIS OF ILE-518; ILE-522; PHE-526; LEU-527; LEU-530; LEU-531 AND 526-PHE--LEU-531.
  16. "Expression of calcineurin B homologous protein 2 protects serum deprivation-induced cell death by serum-independent activation of Na+/H+ exchanger."
    Pang T., Wakabayashi S., Shigekawa M.
    J. Biol. Chem. 277:43771-43777(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CHP2.
  17. "The Na+/H+ exchanger cytoplasmic tail: structure, function, and interactions with tescalcin."
    Li X., Liu Y., Kay C.M., Muller-Esterl W., Fliegel L.
    Biochemistry 42:7448-7456(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TESC AND CALMODULIN.
  18. "Role of calcineurin B homologous protein in pH regulation by the Na+/H+ exchanger 1: tightly bound Ca2+ ions as important structural elements."
    Pang T., Hisamitsu T., Mori H., Shigekawa M., Wakabayashi S.
    Biochemistry 43:3628-3636(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PH REGULATION, INTERACTION WITH CHP1, SUBCELLULAR LOCATION.
  19. "Proline residues in transmembrane segment IV are critical for activity, expression and targeting of the Na+/H+ exchanger isoform 1."
    Slepkov E.R., Chow S., Lemieux M.J., Fliegel L.
    Biochem. J. 379:31-38(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF PRO-167 AND PRO-168.
  20. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic kidney.
  21. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-703, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Platelet.
  22. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-697; SER-703; SER-723; SER-726; SER-729 AND SER-785, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  23. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-703, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  24. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-703, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  25. "Nuclear accumulation of calcineurin B homologous protein 2 (CHP2) results in enhanced proliferation of tumor cells."
    Li Q.H., Wang L.H., Lin Y.N., Chang G.Q., Li H.W., Jin W.N., Hu R.H., Pang T.X.
    Genes Cells 16:416-426(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CHP2, SUBCELLULAR LOCATION.
  26. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-703, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  27. "Structural and functional characterization of transmembrane segment IV of the NHE1 isoform of the Na+/H+ exchanger."
    Slepkov E.R., Rainey J.K., Li X., Liu Y., Cheng F.J., Lindhout D.A., Sykes B.D., Fliegel L.
    J. Biol. Chem. 280:17863-17872(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 155-180, MUTAGENESIS OF PHE-155; LEU-156; GLN-157; SER-158; ASP-159; VAL-160; PHE-161; PHE-162; LEU-163; PHE-164; LEU-165; LEU-166; PRO-167; PRO-168; ILE-169; ILE-170; LEU-171; ASP-172; ALA-173; GLY-174; TYR-175; PHE-176 AND LEU-177.
  28. "Crystallization and preliminary crystallographic analysis of the human calcineurin homologous protein CHP2 bound to the cytoplasmic region of the Na+/H+ exchanger NHE1."
    Ben Ammar Y., Takeda S., Sugawara M., Miyano M., Mori H., Wakabayashi S.
    Acta Crystallogr. F 61:956-958(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PRELIMINARY X-RAY CRYSTALLOGRAPHY OF 503-545 IN COMPLEX WITH CHP2.
  29. "Crystal structure of CHP2 complexed with NHE1-cytosolic region and an implication for pH regulation."
    Ammar Y.B., Takeda S., Hisamitsu T., Mori H., Wakabayashi S.
    EMBO J. 25:2315-2325(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 503-545 IN COMPLEX WITH CHP2, MUTAGENESIS OF ILE-534 AND ILE-537.
  30. "Solution structure of the cytoplasmic region of Na+/H+ exchanger 1 complexed with essential cofactor calcineurin B homologous protein 1."
    Mishima M., Wakabayashi S., Kojima C.
    J. Biol. Chem. 282:2741-2751(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 503-545 IN COMPLEX WITH CHP1.

Entry informationi

Entry nameiSL9A1_HUMAN
AccessioniPrimary (citable) accession number: P19634
Secondary accession number(s): B1ALD6, D3DPL4, Q96EM2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: November 1, 1991
Last modified: February 4, 2015
This is version 167 of the entry and version 2 of the sequence. [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

Miscellaneous

Inhibited by amiloride and 5-amino-substituted derivatives and activated in a cooperative fashion by intracellular H+. In quiescent cells upon growth factor stimulation, the apparent affinity for internal H+ is increased, resulting in a persistent rise in cytoplasmic pH.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.