Sodium/hydrogen exchanger 1 - Slc9a1 - Rattus norvegicus (Rat)

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P26431 (SL9A1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. History...

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

Documents (1) |

Third-party data

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

Names and origin

Protein names

Recommended name:
Sodium/hydrogen exchanger 1

Alternative name(s):
Na(+)/H(+) exchanger 1
Short name=NHE-1
Solute carrier family 9 member 1

Gene names

Name:	Slc9a1
Synonyms:	Nhe1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	820 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	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 similarity. Oligomer. Interacts with CHP1, CHP2 and TESC. Ref.3 Ref.4 Ref.5
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. Note: Colocalizes with and CHP2 at the plasma membrane By similarity. Colocalizes with CHP1 at the reticulum endoplasmic and plasma membrane.
Tissue specificity	Not tissue specific.
Post-translational modification	N-glycosylated and O-glycosylated in the N-terminal region. Ref.2 Ref.5 Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1. Ref.5
Sequence similarities	Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. [View classification]
Caution	The region between transmembrane regions M4 and M5 and between M6 and M7 (also termed intracellular loops IL2 and IL4, respectively) seem to be localized at least in part in the membrane. The hydrophobic region H10 is proposed to be located within the membrane. Although Ref.4 show that TESC-binding results in the maturation and accumulation of SLC9A1 at the cell surface, previous studies with human SLC9A1 report that TESC-binding results in a decrease in activity. Although Ref.4 show that they CHP1 and TESC bind at the same C-terminal site, previous studies with human SLC9A1 report that they bind to different sites.

Ontologies

Keywords
Biological process	Antiport Ion transport Sodium transport Transport
Cellular component	Cell membrane Endoplasmic reticulum Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Calmodulin-binding Sodium
PTM	Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle cell contraction Inferred from expression pattern PubMed 20868366. Source: RGD cardiac muscle cell differentiation Inferred from electronic annotation. Source: Ensembl cell differentiation Inferred from expression pattern PubMed 16495213. Source: RGD cell growth Inferred from expression pattern PubMed 15452191. Source: RGD cellular response to acidity Inferred from sequence or structural similarity. Source: UniProtKB cellular response to antibiotic Inferred from expression pattern PubMed 20868366. Source: RGD cellular response to electrical stimulus Inferred from expression pattern PubMed 20868366. Source: RGD cellular response to hypoxia Inferred from direct assay PubMed 20868366. Source: RGD cellular response to insulin stimulus Inferred from direct assay PubMed 20868366. Source: RGD cellular response to organic cyclic compound Inferred from expression pattern PubMed 20868366. Source: RGD negative regulation of apoptotic process Inferred from mutant phenotype PubMed 17552965. Source: RGD neuron death Inferred from mutant phenotype PubMed 19328212. Source: RGD positive regulation of action potential Inferred from mutant phenotype PubMed 18319243. Source: RGD positive regulation of cell growth Inferred from mutant phenotype PubMed 19687166. Source: RGD positive regulation of intracellular signal transduction Inferred from mutant phenotype PubMed 14600156. Source: RGD positive regulation of mitochondrial membrane permeability Inferred from mutant phenotype PubMed 21297023. Source: RGD regulation of intracellular pH Inferred from sequence or structural similarity. Source: UniProtKB regulation of pH Inferred from sequence or structural similarity. Source: UniProtKB regulation of sensory perception of pain Inferred from mutant phenotype PubMed 21763398. Source: RGD regulation of the force of heart contraction Inferred from mutant phenotype PubMed 21659487. Source: RGD response to acid Inferred from sequence or structural similarity. Source: UniProtKB response to acidity Inferred from direct assay Ref.4. Source: UniProtKB response to drug Inferred from expression pattern PubMed 15452191. Source: RGD response to organic cyclic compound Inferred from direct assay PubMed 17308111. Source: RGD sodium ion export Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	T-tubule Inferred from direct assay PubMed 20868366. Source: RGD basolateral plasma membrane Inferred from direct assay PubMed 9438178. Source: RGD cell surface Inferred from direct assay PubMed 20868366. Source: RGD cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB endoplasmic reticulum Inferred from direct assay Ref.5. Source: UniProtKB endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral component of membrane Inferred from electronic annotation. Source: UniProtKB-KW intercalated disc Inferred from direct assay PubMed 20868366. Source: RGD membrane raft Inferred from direct assay PubMed 16002403. Source: RGD mitochondrion Inferred from direct assay PubMed 21297023. Source: RGD perinuclear region of cytoplasm Inferred from direct assay PubMed 20868366. Source: RGD plasma membrane Inferred from direct assay Ref.4 Ref.5. Source: UniProtKB sarcolemma Inferred from direct assay PubMed 20868366. Source: RGD
Molecular_function	calcium-dependent protein binding Inferred from sequence or structural similarity. Source: UniProtKB protein binding Inferred from physical interaction Ref.4. Source: UniProtKB sodium:proton antiporter activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Chp2	Q810D1	2	EBI-77471,EBI-6146708

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 820

820

Sodium/hydrogen exchanger 1

PRO_0000052351

Regions

Topological domain

1 – 12

Cytoplasmic Potential

Transmembrane

13 – 33

Helical; Name=M1; Potential

Topological domain

34 – 105

Extracellular Potential

Transmembrane

106 – 131

Helical; Name=M2; Potential

Topological domain

132 – 133

Cytoplasmic Potential

Transmembrane

134 – 153

Helical; Name=M3; Potential

Topological domain

154 – 158

Extracellular Potential

Transmembrane

159 – 178

Helical; Name=M4; Potential

Topological domain

179 – 195

Cytoplasmic Potential

Transmembrane

196 – 215

Helical; Name=M5; Potential

Topological domain

216 – 231

Extracellular Potential

Transmembrane

232 – 251

Helical; Name=M6; Potential

Topological domain

252 – 260

Cytoplasmic Potential

Transmembrane

261 – 280

Helical; Name=M7; Potential

Topological domain

281 – 298

Extracellular Potential

Transmembrane

299 – 319

Helical; Name=M8; Potential

Topological domain

320 – 342

Cytoplasmic Potential

Transmembrane

343 – 362

Helical; Name=M9; Potential

Topological domain

363 – 385

Extracellular Potential

Intramembrane

386 – 406

Name=H10; By similarity

Topological domain

407 – 414

Extracellular Potential

Transmembrane

415 – 434

Helical; Name=M10; Potential

Topological domain

435 – 452

Cytoplasmic Potential

Transmembrane

453 – 474

Helical; Name=M11; Potential

Topological domain

475 – 483

Extracellular Potential

Transmembrane

484 – 503

Helical; Name=M12; Potential

Topological domain

504 – 820

317

Cytoplasmic Potential

Region

520 – 543

Interaction with CHP2 By similarity

Sites

Site

165

Channel pore-lining By similarity

Amino acid modifications

Modified residue

603

Phosphoserine By similarity

Modified residue

609

Phosphoserine By similarity

Modified residue

697

Phosphoserine By similarity

Modified residue

701

Phosphoserine By similarity

Modified residue

707

Phosphoserine By similarity

Modified residue

727

Phosphoserine By similarity

Modified residue

730

Phosphoserine By similarity

Modified residue

733

Phosphoserine By similarity

Modified residue

790

Phosphoserine By similarity

Glycosylation

374

N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis

522 – 538

INEEI…LLTGI → QNEEQHTQQLDHQQTGQ: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. Ref.5

Mutagenesis

530 – 535

FLDHLL → AADHAA: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. Ref.4

Mutagenesis

530 – 535

FLDHLL → QQDHQQ: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. Ref.4

Mutagenesis

530 – 535

FLDHLL → RRDHRR: Abolishes interaction with TESC and markedly reduces transporter activity. Does not alter its cell membrane localization. Ref.4

Sequences

Sequence

Length

Mass (Da)

Tools

P26431 [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: 58398DE74A9642FB
Show »

FASTA

820

91,647

        10         20         30         40         50         60 
MMLRWSGIWG LYPPRIFPSL LVVVALVGLL PVLRSHGLQL NPTASTIRGS EPPRERSIGD 

        70         80         90        100        110        120 
VTTAPSEPLH HPDDRNLTNL YIEHGAKPVR KAFPVLDIDY LHVRTPFEIS LWILLACLMK 

       130        140        150        160        170        180 
IGFHVIPTIS SIVPESCLLI VVGLLVGGLI KGVGETPPFL QSDVFFLFLL PPIILDAGYF 

       190        200        210        220        230        240 
LPLRQFTENL GTILIFAVVG TLWNAFFLGG LLYAVCLVGG EQINNIGLLD TLLFGSIISA 

       250        260        270        280        290        300 
VDPVAVLAVF EEIHINELLH ILVFGESLLN DAVTVVLYHL FEEFASYEYV GISDIFLGFL 

       310        320        330        340        350        360 
SFFVVSLGGV FVGVVYGVIA AFTSRFTSHI RVIEPLFVFL YSYMAYLSAE LFHLSGIMAL 

       370        380        390        400        410        420 
IASGVVMRPY VEANISHKSH TTIKYFLKMW SSVSETLIFI FLGVSTVAGS HQWNWTFVIS 

       430        440        450        460        470        480 
TLLFCLIARV LGVLVLTWFI NKFRIVKLTP KDQFIIAYGG LRGAIAFSLG YLLDKKHFPM 

       490        500        510        520        530        540 
CDLFLTAIIT VIFFTVFVQG MTIRPLVDLL AVKKKQETKR SINEEIHTQF LDHLLTGIED 

       550        560        570        580        590        600 
ICGHYGHHHW KDKLNRFNKK YVKKCLIAGE RSKEPQLIAF YHKMEMKQAI ELVESGGMGK 

       610        620        630        640        650        660 
IPSAVSTVSM QNIHPKSAAS ERILPALSKD KEEEIRKILR SNLQKTRQRL RSYNRHTLVA 

       670        680        690        700        710        720 
DPYEEAWNQM LLRRQKARQL EQKITNYLTV PAHKLDSPTM SRARIGSDPL AYEPKADLPV 

       730        740        750        760        770        780 
ITIDPASPQS PESVDLVNEE LKGKVLGLKR GPRTTPEEEE EDEDGVIMIR SKEPSSPGTD 

       790        800        810        820 
DVFTPGPSDS PGSQRIQRCL SDPGPHPEPG EGEPFIPKGQ

« Hide

References

[1]	"Molecular cloning of putative members of the Na/H exchanger gene family. cDNA cloning, deduced amino acid sequence, and mRNA tissue expression of the rat Na/H exchanger NHE-1 and two structurally related proteins." Orlowski J., Kandasamy R.A., Shull G.E. J. Biol. Chem. 267:9331-9339(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Heart.
[2]	"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: GLYCOSYLATION.
[3]	"Calcineurin homologous protein isoform 2 (CHP2), Na+/H+ exchangers-binding protein, is expressed in intestinal epithelium." Inoue H., Nakamura Y., Nagita M., Takai T., Masuda M., Nakamura N., Kanazawa H. Biol. Pharm. Bull. 26:148-155(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CHP1 AND CHP2.
[4]	"Calcineurin B homologous protein 3 promotes the biosynthetic maturation, cell surface stability, and optimal transport of the Na+/H+ exchanger NHE1 isoform." Zaun H.C., Shrier A., Orlowski J. J. Biol. Chem. 283:12456-12467(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TESC, MUTAGENESIS OF 530-PHE--LEU-535.
[5]	"Dual functional significance of calcineurin homologous protein 1 binding to Na(+)/H(+) exchanger isoform 1." Matsushita M., Tanaka H., Mitsui K., Kanazawa H. Am. J. Physiol. 301:C280-C288(2011) [PubMed] [Europe PMC] [Abstract] Cited for: OLIGOMERIZATION, GLYCOSYLATION, UBIQUITINATION, MUTAGENESIS OF 522-ILE--ILE-538.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M85299 mRNA. Translation: AAA98479.1.
PIR	A40204.
RefSeq	NP_036784.1. NM_012652.1.
UniGene	Rn.5025.
3D structure databases
ProteinModelPortal	P26431.
SMR	P26431. Positions 159-184, 254-279, 342-369, 507-549.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
IntAct	P26431. 3 interactions.
STRING	10116.ENSRNOP00000011049.
Chemistry
BindingDB	P26431.
ChEMBL	CHEMBL2577.
Protein family/group databases
TCDB	2.A.36.1.1. the monovalent cation:proton antiporter-1 (cpa1) family.
PTM databases
PhosphoSite	P26431.
Proteomic databases
PaxDb	P26431.
PRIDE	P26431.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000011049; ENSRNOP00000011049; ENSRNOG00000007982.
GeneID	24782.
KEGG	rno:24782.
UCSC	RGD:3718. rat.
Organism-specific databases
CTD	6548.
RGD	3718. Slc9a1.
Phylogenomic databases
eggNOG	COG0025.
GeneTree	ENSGT00560000077158.
HOGENOM	HOG000247044.
HOVERGEN	HBG052615.
InParanoid	P26431.
KO	K05742.
OMA	YDRVGIV.
OrthoDB	EOG7XWPN4.
PhylomeDB	P26431.
TreeFam	TF317212.
Gene expression databases
Genevestigator	P26431.
Family and domain databases
InterPro	IPR006153. Cation/H_exchanger. IPR018422. Cation/H_exchanger_CPA1. IPR001970. Na/H_exchanger_1. IPR004709. NaH_exchanger. [Graphical view]
PANTHER	PTHR10110. PTHR10110. 1 hit.
Pfam	PF00999. Na_H_Exchanger. 1 hit. [Graphical view]
PRINTS	PR01084. NAHEXCHNGR. PR01085. NAHEXCHNGR1.
TIGRFAMs	TIGR00840. b_cpa1. 1 hit.
ProtoNet	Search...
Other
NextBio	604392.
PRO	P26431.

Entry information

Entry name

SL9A1_RAT

Accession

Primary (citable) accession number: P26431

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	October 1, 1996
Last modified:	July 9, 2014
This is version 130 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

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

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry

Protein family/group databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents