Sodium/hydrogen exchanger 3 - Homo sapiens (Human)

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P48764 (SL9A3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 112. History...

Clusters with 100%, 90%, 50% identity |

Documents (5) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Sodium/hydrogen exchanger 3

Alternative name(s):
Na(+)/H(+) exchanger 3
Short name=NHE-3
Solute carrier family 9 member 3

Gene names

Name:	SLC9A3
Synonyms:	NHE3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	834 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	Binds SLC9A3R1 and SLC9A3R2. Interacts with CHP1, CHP2 and SHANK2. Interacts with PDZD3 and interactions decrease in response to elevated calcium ion levels By similarity. Ref.4
Subcellular location	Cell membrane; Multi-pass membrane protein. Note: In intestinal epithelial cells, localizes to the ileal brush border. Phosphorylation at Ser-663 by SGK1 is associated with increased abundance at the cell membrane. Ref.4
Post-translational modification	Phosphorylated by PKA, which inhibits activity By similarity. Phosphorylation at Ser-663 by SGK1 is associated with increased abundance at the cell membrane By similarity.
Sequence similarities	Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. [View classification]
Caution	The number, localization and denomination of hydrophobic domains in the Na⁺/H⁺ exchangers vary among authors.

Ontologies

Keywords
Biological process	Antiport Ion transport Sodium transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of pH Inferred from electronic annotation. Source: Compara
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara brush border Inferred from sequence or structural similarity. Source: UniProtKB cell surface Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	sodium:hydrogen antiporter activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 834

834

Sodium/hydrogen exchanger 3

PRO_0000052356

Regions

Topological domain

1 – 12

Cytoplasmic Potential

Intramembrane

13 – 24

Name=A/M1; Potential

Topological domain

25 – 54

Cytoplasmic Potential

Intramembrane

55 – 73

Name=B/M2; Potential

Topological domain

74 – 79

Cytoplasmic Potential

Transmembrane

80 – 99

Helical; Name=C/M3; Potential

Topological domain

100 – 112

Extracellular Potential

Transmembrane

113 – 133

Helical; Name=D/M4; Potential

Topological domain

134 – 139

Cytoplasmic Potential

Transmembrane

140 – 160

Helical; Name=E/M5; Potential

Topological domain

161 – 180

Extracellular Potential

Transmembrane

181 – 202

Helical; Name=F/M5A; Potential

Topological domain

203 – 210

Cytoplasmic Potential

Transmembrane

211 – 232

Helical; Name=G/M5B; Potential

Topological domain

233 – 252

Extracellular Potential

Transmembrane

253 – 274

Helical; Name=H/M6; Potential

Topological domain

275 – 290

Cytoplasmic Potential

Transmembrane

291 – 309

Helical; Name=I/M7; Potential

Topological domain

310 – 340

Extracellular Potential

Transmembrane

341 – 362

Helical; Name=J/M8; Potential

Topological domain

363 – 369

Cytoplasmic Potential

Transmembrane

370 – 390

Helical; Name=K/M9; Potential

Topological domain

391 – 405

Extracellular Potential

Intramembrane

406 – 426

Name=L; Potential

Topological domain

427 – 435

Extracellular Potential

Transmembrane

436 – 456

Helical; Name=M/M10; Potential

Topological domain

457 – 834

378

Cytoplasmic Potential

Region

590 – 667

Interaction with PDZD3 By similarity

Amino acid modifications

Modified residue

555

Phosphoserine By similarity

Modified residue

607

Phosphoserine By similarity

Modified residue

663

Phosphoserine; by SGK1

Glycosylation

241

N-linked (GlcNAc...) Potential

Glycosylation

326

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

799

C → R. Ref.1 Ref.3
Corresponds to variant rs2247114 [ dbSNP | Ensembl ].

VAR_060593

Sequences

Sequence

Length

Mass (Da)

Tools

P48764 [UniParc].

Last modified November 24, 2009. Version 2.
Checksum: 3E7CE3267F6E86F7
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FASTA

834

92,855

        10         20         30         40         50         60 
MWGLGARGPD RGLLLALALG GLARAGGVEV EPGGAHGESG GFQVVTFEWA HVQDPYVIAL 

        70         80         90        100        110        120 
WILVASLAKI GFHLSHKVTS VVPESALLIV LGLVLGGIVW AADHIASFTL TPTVFFFYLL 

       130        140        150        160        170        180 
PPIVLDAGYF MPNRLFFGNL GTILLYAVVG TVWNAATTGL SLYGVFLSGL MGDLQIGLLD 

       190        200        210        220        230        240 
FLLFGSLMAA VDPVAVLAVF EEVHVNEVLF IIVFGESLLN DAVTVVLYNV FESFVALGGD 

       250        260        270        280        290        300 
NVTGVDCVKG IVSFFVVSLG GTLVGVVFAF LLSLVTRFTK HVRIIEPGFV FIISYLSYLT 

       310        320        330        340        350        360 
SEMLSLSAIL AITFCGICCQ KYVKANISEQ SATTVRYTMK MLASSAETII FMFLGISAVN 

       370        380        390        400        410        420 
PFIWTWNTAF VLLTLVFISV YRAIGVVLQT WLLNRYRMVQ LEPIDQVVLS YGGLRGAVAF 

       430        440        450        460        470        480 
ALVVLLDGDK VKEKNLFVST TIIVVFFTVI FQGLTIKPLV QWLKVKRSEH REPRLNEKLH 

       490        500        510        520        530        540 
GRAFDHILSA IEDISGQIGH NYLRDKWSHF DRKFLSRVLM RRSAQKSRDR ILNVFHELNL 

       550        560        570        580        590        600 
KDAISYVAEG ERRGSLAFIR SPSTDNVVNV DFTPRSSTVE ASVSYLLREN VSAVCLDMQS 

       610        620        630        640        650        660 
LEQRRRSIRD AEDMVTHHTL QQYLYKPRQE YKHLYSRHEL TPTEDEKQDR EIFHRTMRKR 

       670        680        690        700        710        720 
LESFKSTKLG LNQNKKAAKL YKRERAQKRR NSSIPNGKLP MESPAQNFTI KEKDLELSDT 

       730        740        750        760        770        780 
EEPPNYDEEM SGGIEFLASV TKDTASDSPA GIDNPVFSPD EALDRSLLAR LPPWLSPGET 

       790        800        810        820        830 
VVPSQRARTQ IPYSPGTFCR LMPFRLSSKS VDSFLQADGP EERPPAALPE STHM

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, tissue distribution, and functional analysis of the human Na+/N+ exchanger isoform, NHE3." Brant S.R., Yun C.H., Donowitz M., Tse C.-M. Am. J. Physiol. 269:C198-C206(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-799. Tissue: Kidney cortex.
[2]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. Rubin E.M. Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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], VARIANT ARG-799. Tissue: Colon.
[4]	"Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4) dependent mechanism." Zachos N.C., Hodson C., Kovbasnjuk O., Li X., Thelin W.R., Cha B., Milgram S., Donowitz M. Cell. Physiol. Biochem. 22:693-704(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PDZD3.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U28043 mRNA. Translation: AAB48990.1. AC010442 Genomic DNA. No translation available. AC106772 Genomic DNA. No translation available. BC101669 mRNA. Translation: AAI01670.1. BC101671 mRNA. Translation: AAI01672.1.
IPI	IPI00011184.
PIR	B40205.
RefSeq	NP_004165.2. NM_004174.2.
UniGene	Hs.658120.
3D structure databases
ProteinModelPortal	P48764.
SMR	P48764. Positions 179-207, 607-669.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1787470.
STRING	9606.ENSP00000264938.
PTM databases
PhosphoSite	P48764.
Polymorphism databases
DMDM	269849652.
Proteomic databases
PaxDb	P48764.
PRIDE	P48764.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264938; ENSP00000264938; ENSG00000066230.
GeneID	6550.
KEGG	hsa:6550.
UCSC	uc003jbe.2. human.
Organism-specific databases
CTD	6550.
GeneCards	GC05M000473.
H-InvDB	HIX0004707. HIX0032039.
HGNC	HGNC:11073. SLC9A3.
HPA	HPA036493. HPA036669.
MIM	182307. gene.
neXtProt	NX_P48764.
PharmGKB	PA316.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0025.
HOGENOM	HOG000247044.
HOVERGEN	HBG052615.
InParanoid	P48764.
KO	K12040.
OMA	RDKWSNF.
OrthoDB	EOG4BVRT8.
PhylomeDB	P48764.
Enzyme and pathway databases
Pathway_Interaction_DB	endothelinpathway. Endothelins.
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P48764.
Bgee	P48764.
CleanEx	HS_SLC9A3.
Genevestigator	P48764.
GermOnline	ENSG00000066230. Homo sapiens.
Family and domain databases
InterPro	IPR006153. Cation/H_exchanger. IPR018422. Cation/H_exchanger_CPA1. IPR018410. Na/H_exchanger_3/5. IPR004709. NaH_exchanger. [Graphical view]
PANTHER	PTHR10110. PTHR10110. 1 hit.
Pfam	PF00999. Na_H_Exchanger. 1 hit. [Graphical view]
PRINTS	PR01084. NAHEXCHNGR. PR01087. NAHEXCHNGR3.
TIGRFAMs	TIGR00840. b_cpa1. 1 hit.
ProtoNet	Search...
Other
ChEMBL	CHEMBL3273.
GenomeRNAi	6550.
NextBio	25493.
SOURCE	Search...

Entry information

Entry name

SL9A3_HUMAN

Accession

Primary (citable) accession number: P48764
Secondary accession number(s): Q3MIW3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	November 24, 2009
Last modified:	April 3, 2013
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.

Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents