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P19634 (SL9A1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 158. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SLC9A1
Synonyms:APNH1, NHE1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length815 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Ref.11 Ref.15 Ref.18

Subunit structure

Oligomer By similarity. Interacts with calmodulin and TESC. Interacts (via the juxtamembrane region of the cytoplasmic C-terminus 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. Ref.10 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.25

Subcellular location

Membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; 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. Ref.14 Ref.18 Ref.25

Tissue specificity

Kidney and intestine.

Post-translational modification

O-glycosylated. Ref.9

Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1 By similarity.

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.

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.17 report that TESC-binding results in a decrease in activity, studies with rat SLC9A1 show that TESC-binding results in the maturation and accumulation of SLC9A1 at the cell surface.

Although Ref.17 report that CHP1 and TESC bind to SLC9A1 at different sites, studies with rat SLC9A1 show that they bind at the same C-terminal site.

Biophysicochemical properties

pH dependence:

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

Ontologies

Keywords
   Biological processAntiport
Ion transport
Sodium transport
Transport
   Cellular componentCell membrane
Endoplasmic reticulum
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandCalmodulin-binding
Sodium
   PTMGlycoprotein
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcarbohydrate metabolic process

Traceable author statement. Source: Reactome

cardiac muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

cell growth

Inferred from electronic annotation. Source: Ensembl

cellular response to acidity

Inferred from sequence or structural similarity. Source: UniProtKB

glycosaminoglycan metabolic process

Traceable author statement. Source: Reactome

hyaluronan catabolic process

Traceable author statement. Source: Reactome

hyaluronan metabolic process

Traceable author statement. Source: Reactome

hydrogen ion transmembrane transport

Traceable author statement Ref.1. Source: GOC

ion transport

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

neuron death

Inferred from electronic annotation. Source: Ensembl

positive regulation of action potential

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of mitochondrial membrane permeability

Inferred from electronic annotation. Source: Ensembl

protein oligomerization

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of intracellular pH

Inferred from direct assay Ref.18. Source: UniProtKB

regulation of pH

Inferred from direct assay Ref.11. Source: UniProtKB

regulation of sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

regulation of the force of heart contraction

Inferred from electronic annotation. Source: Ensembl

response to acid

Inferred from direct assay Ref.11. Source: UniProtKB

response to acidity

Inferred from direct assay Ref.11. Source: UniProtKB

response to drug

Inferred from electronic annotation. Source: Ensembl

response to organic cyclic compound

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

sodium ion export

Inferred from sequence or structural similarity. Source: UniProtKB

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentbasolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 21553168. Source: UniProtKB

endoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

integral component of membrane

Traceable author statement Ref.4. Source: UniProtKB

membrane raft

Inferred from electronic annotation. Source: Ensembl

mitochondrion

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay. Source: HPA

plasma membrane

Inferred from direct assay Ref.18PubMed 21553168. Source: UniProtKB

   Molecular_functioncalcium-dependent protein binding

Inferred from direct assay Ref.18. Source: UniProtKB

sodium:hydrogen antiporter activity

Inferred from direct assay Ref.15Ref.11. Source: UniProtKB

solute:hydrogen antiporter activity

Traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P19634-1)

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.
Isoform 2 (identifier: P19634-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 815815Sodium/hydrogen exchanger 1
PRO_0000052347

Regions

Topological domain1 – 1212Cytoplasmic Potential
Transmembrane13 – 3321Helical; Name=M1; Potential
Topological domain34 – 10572Extracellular Potential
Transmembrane106 – 12722Helical; Name=M2; Potential
Topological domain128 – 1292Cytoplasmic Potential
Transmembrane130 – 14920Helical; Name=M3; Potential
Topological domain150 – 1545Extracellular Potential
Transmembrane155 – 17420Helical; Name=M4; Potential
Topological domain175 – 19117Cytoplasmic Potential
Transmembrane192 – 21120Helical; Name=M5; Potential
Topological domain212 – 22716Extracellular Potential
Transmembrane228 – 24720Helical; Name=M6; Potential
Topological domain248 – 2569Cytoplasmic Potential
Transmembrane257 – 27620Helical; Name=M7; Potential
Topological domain277 – 29418Extracellular Potential
Transmembrane295 – 31521Helical; Name=M8; Potential
Topological domain316 – 33823Cytoplasmic Potential
Transmembrane339 – 35820Helical; Name=M9; Potential
Topological domain359 – 38123Extracellular Potential
Intramembrane382 – 40221Name=H10; By similarity
Topological domain403 – 4108Extracellular Potential
Transmembrane411 – 43020Helical; Name=M10; Potential
Topological domain431 – 44818Cytoplasmic Potential
Transmembrane449 – 47022Helical; Name=M11; Potential
Topological domain471 – 4799Extracellular Potential
Transmembrane480 – 49920Helical; Name=M12; Potential
Topological domain500 – 815316Cytoplasmic Potential
Region516 – 53924Interaction with CHP2

Sites

Site1611Channel pore-lining Probable
Site3701Not glycosylated

Amino acid modifications

Modified residue5991Phosphoserine By similarity
Modified residue6051Phosphoserine By similarity
Modified residue6931Phosphoserine By similarity
Modified residue6971Phosphoserine Ref.22
Modified residue7031Phosphoserine Ref.21 Ref.22 Ref.23 Ref.24 Ref.26
Modified residue7231Phosphoserine Ref.22
Modified residue7261Phosphoserine Ref.22
Modified residue7291Phosphoserine Ref.22
Modified residue7851Phosphoserine Ref.22
Glycosylation751N-linked (GlcNAc...) Ref.9

Natural variations

Alternative sequence496 – 55459GMTIR…LNRFN → VLGQGRAGPCLGDPHRLFPW KERKACDLKCDSSPSSTTNL LCDLGRATPPFWASVSSIVK in isoform 2.
VSP_022101
Alternative sequence555 – 815261Missing in isoform 2.
VSP_022102
Natural variant6821N → K.
Corresponds to variant rs35703140 [ dbSNP | Ensembl ].
VAR_050231

Experimental info

Mutagenesis1551F → C: Almost complete loss of activity. Ref.27
Mutagenesis1561L → C: Almost complete loss of activity. Ref.27
Mutagenesis1571Q → C: Reduces activity. Ref.27
Mutagenesis1581S → C: Almost complete loss of activity. Ref.27
Mutagenesis1591D → C: Almost complete loss of activity. Ref.27
Mutagenesis1601V → C: Reduces activity. Ref.27
Mutagenesis1611F → C: Reduces activity. Ref.27
Mutagenesis1621F → C: Almost complete loss of activity. Ref.27
Mutagenesis1631L → C: Reduces activity. Ref.27
Mutagenesis1641F → C: Almost complete loss of activity. Ref.27
Mutagenesis1651L → C: Reduces activity. Ref.27
Mutagenesis1661L → C: Reduces activity. Ref.27
Mutagenesis1671P → A: Reduces activity. Ref.19 Ref.27
Mutagenesis1671P → C or G: Almost complete loss of activity. Reduces membrane localization. Ref.19 Ref.27
Mutagenesis1681P → A or C: Almost complete loss of activity. Ref.19 Ref.27
Mutagenesis1681P → G: Reduces activity. Ref.19 Ref.27
Mutagenesis1691I → C: Reduces activity. Ref.27
Mutagenesis1701I → C: Reduces activity. Ref.27
Mutagenesis1711L → C: Reduces activity. Ref.27
Mutagenesis1721D → C: Almost complete loss of activity. Ref.27
Mutagenesis1731A → C: Reduces activity. Ref.27
Mutagenesis1741G → C: Reduces activity. Ref.27
Mutagenesis1751Y → C: Almost complete loss of activity. Ref.27
Mutagenesis1761F → C: Almost complete loss of activity. Ref.27
Mutagenesis1771L → C: Reduces activity. Ref.27
Mutagenesis1781P → A: No effect.
Mutagenesis1801R → C: Reduces activity. Ref.13
Mutagenesis1811Q → C: Reduces activity. Ref.13
Mutagenesis5181I → Q: Reduces interaction with CHP1 and the exchange activity; when associated with Q-522. Ref.15
Mutagenesis5221I → Q: Reduces interaction with CHP1 and the exchange activity; when associated with Q-518. Ref.15
Mutagenesis526 – 5316FLDHLL → QQDHQQ: Inhibits interaction with CHP1 and the exchange activity. CHPI does not localize at the cell membrane. Ref.15
Mutagenesis526 – 5316FLDHLL → RRDHRR: Inhibits interaction with CHP1 and the exchange activity. CHPI does not localize at the cell membrane. Ref.15
Mutagenesis5261F → Q: Reduces interaction with CHP1 and the exchange activity; when associated with Q-527. Ref.15
Mutagenesis5271L → Q: Reduces interaction with CHP1 and the exchange activity; when associated with Q-526. Ref.15
Mutagenesis5301L → Q: Reduces interaction with CHP1 and the exchange activity; when associated with Q-531. Ref.15
Mutagenesis5311L → Q: Reduces interaction with CHP1 and the exchange activity; when associated with Q-530. Ref.15
Mutagenesis5341I → D or K: Strongly reduced interaction with CHP2. Ref.29
Mutagenesis5371I → K: Strongly reduced interaction with CHP2. Ref.29

Secondary structure

....................... 815
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1991. Version 2.
Checksum: 02EC748C79DF6526

FASTA81590,763
        10         20         30         40         50         60 
MVLRSGICGL SPHRIFPSLL VVVALVGLLP VLRSHGLQLS PTASTIRSSE PPRERSIGDV 

        70         80         90        100        110        120 
TTAPPEVTPE SRPVNHSVTD HGMKPRKAFP VLGIDYTHVR TPFEISLWIL LACLMKIGFH 

       130        140        150        160        170        180 
VIPTISSIVP ESCLLIVVGL LVGGLIKGVG ETPPFLQSDV FFLFLLPPII LDAGYFLPLR 

       190        200        210        220        230        240 
QFTENLGTIL IFAVVGTLWN AFFLGGLMYA VCLVGGEQIN NIGLLDNLLF GSIISAVDPV 

       250        260        270        280        290        300 
AVLAVFEEIH INELLHILVF GESLLNDAVT VVLYHLFEEF ANYEHVGIVD IFLGFLSFFV 

       310        320        330        340        350        360 
VALGGVLVGV VYGVIAAFTS RFTSHIRVIE PLFVFLYSYM AYLSAELFHL SGIMALIASG 

       370        380        390        400        410        420 
VVMRPYVEAN ISHKSHTTIK YFLKMWSSVS ETLIFIFLGV STVAGSHHWN WTFVISTLLF 

       430        440        450        460        470        480 
CLIARVLGVL GLTWFINKFR IVKLTPKDQF IIAYGGLRGA IAFSLGYLLD KKHFPMCDLF 

       490        500        510        520        530        540 
LTAIITVIFF TVFVQGMTIR PLVDLLAVKK KQETKRSINE EIHTQFLDHL LTGIEDICGH 

       550        560        570        580        590        600 
YGHHHWKDKL NRFNKKYVKK CLIAGERSKE PQLIAFYHKM EMKQAIELVE SGGMGKIPSA 

       610        620        630        640        650        660 
VSTVSMQNIH PKSLPSERIL PALSKDKEEE IRKILRNNLQ KTRQRLRSYN RHTLVADPYE 

       670        680        690        700        710        720 
EAWNQMLLRR QKARQLEQKI NNYLTVPAHK LDSPTMSRAR IGSDPLAYEP KEDLPVITID 

       730        740        750        760        770        780 
PASPQSPESV DLVNEELKGK VLGLSRDPAK VAEEDEDDDG GIMMRSKETS SPGTDDVFTP 

       790        800        810 
APSDSPSSQR IQRCLSDPGP HPEPGEGEPF FPKGQ 

« Hide

Isoform 2 [UniParc].

Checksum: 961A4B1AEDEA68A5
Show »

FASTA55561,013

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[21]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-703, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[22]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRI57487.
RefSeqNP_003038.2. NM_003047.4.
UniGeneHs.469116.
Hs.91389.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Y4ENMR-A155-180[»]
2BECX-ray2.70B503-545[»]
2E30NMR-B503-545[»]
2HTGNMR-A250-274[»]
2KBVNMR-A447-472[»]
2L0ENMR-A226-250[»]
2YGGX-ray2.23A622-689[»]
ProteinModelPortalP19634.
SMRP19634. Positions 155-180, 250-275, 338-365, 447-472, 503-545, 622-685.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112438. 14 interactions.
IntActP19634. 6 interactions.
MINTMINT-194742.
STRING9606.ENSP00000263980.

Chemistry

BindingDBP19634.
ChEMBLCHEMBL2781.
DrugBankDB00594. Amiloride.

Protein family/group databases

TCDB2.A.36.1.13. the monovalent cation:proton antiporter-1 (cpa1) family.

PTM databases

PhosphoSiteP19634.

Polymorphism databases

DMDM127809.

Proteomic databases

PaxDbP19634.
PRIDEP19634.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263980; ENSP00000263980; ENSG00000090020. [P19634-1]
ENST00000374086; ENSP00000363199; ENSG00000090020. [P19634-2]
GeneID6548.
KEGGhsa:6548.
UCSCuc001bnm.4. human. [P19634-1]
uc001bnn.3. human. [P19634-2]

Organism-specific databases

CTD6548.
GeneCardsGC01M027425.
HGNCHGNC:11071. SLC9A1.
HPACAB022371.
HPA052891.
MIM107310. gene.
neXtProtNX_P19634.
PharmGKBPA35928.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0025.
HOGENOMHOG000247044.
HOVERGENHBG052615.
InParanoidP19634.
KOK05742.
OMAWKERKAC.
OrthoDBEOG7XWPN4.
PhylomeDBP19634.
TreeFamTF317212.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
REACT_15518. Transmembrane transport of small molecules.
SignaLinkP19634.

Gene expression databases

ArrayExpressP19634.
BgeeP19634.
CleanExHS_SLC9A1.
GenevestigatorP19634.

Family and domain databases

InterProIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR001970. Na/H_exchanger_1.
IPR004709. NaH_exchanger.
[Graphical view]
PANTHERPTHR10110. PTHR10110. 1 hit.
PfamPF00999. Na_H_Exchanger. 1 hit.
[Graphical view]
PRINTSPR01084. NAHEXCHNGR.
PR01085. NAHEXCHNGR1.
TIGRFAMsTIGR00840. b_cpa1. 1 hit.
ProtoNetSearch...

Other

ChiTaRSSLC9A1. human.
EvolutionaryTraceP19634.
GeneWikiSodium%E2%80%93hydrogen_antiporter_1.
GenomeRNAi6548.
NextBio25485.
PROP19634.
SOURCESearch...

Entry information

Entry nameSL9A1_HUMAN
AccessionPrimary (citable) accession number: P19634
Secondary accession number(s): B1ALD6, D3DPL4, Q96EM2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: November 1, 1991
Last modified: April 16, 2014
This is version 158 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM