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Q92581 (SL9A6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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 6
Alternative name(s):
Na(+)/H(+) exchanger 6
Short name=NHE-6
Solute carrier family 9 member 6
Gene names
Name:SLC9A6
Synonyms:KIAA0267, NHE6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length669 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Electroneutral exchange of protons for Na+ and K+ across the early and recycling endosome membranes. Contributes to calcium homeostasis.

Subcellular location

Endosome membrane; Multi-pass membrane protein. Note: Is present in the recycling compartments including early and recycling endosomes, and only appears transiently on the plasma membrane. Ref.6

Tissue specificity

Ubiquitous; but is most abundant in mitochondrion-rich tissues such as brain, skeletal muscle and heart.

Involvement in disease

Mental retardation, X-linked, syndromic, Christianson type (MRXSCH) [MIM:300243]: A syndrome characterized by profound mental retardation, epilepsy, ataxia, and microcephaly. It shows phenotypic overlap with Angelman syndrome.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.10

Sequence similarities

Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. [View classification]

Caution

Was originally (Ref.1) identified as a mitochondrial inner membrane protein, but was later shown to be localized in early and recycling endosomes and not mitochondria (Ref.6).

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q92581-1)

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: Q92581-2)

The sequence of this isoform differs from the canonical sequence as follows:
     144-144: V → VNVSGKFYEYMLKGEISSHELNNVQDNEMLRKV
Isoform 3 (identifier: Q92581-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: Missing.
     144-144: V → VNVSGKFYEYMLKGEISSHELNNVQDNEMLRKV
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 669669Sodium/hydrogen exchanger 6
PRO_0000052362

Regions

Transmembrane28 – 4821Helical; Potential
Transmembrane71 – 9121Helical; Potential
Transmembrane103 – 12321Helical; Potential
Transmembrane142 – 16221Helical; Potential
Transmembrane179 – 19921Helical; Potential
Transmembrane220 – 24021Helical; Potential
Transmembrane246 – 26621Helical; Potential
Transmembrane292 – 31221Helical; Potential
Transmembrane340 – 36021Helical; Potential
Transmembrane382 – 40221Helical; Potential
Transmembrane404 – 42421Helical; Potential
Transmembrane447 – 46721Helical; Potential
Transmembrane483 – 50321Helical; Potential

Amino acid modifications

Glycosylation1281N-linked (GlcNAc...) Ref.9
Cross-link443Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.7

Natural variations

Alternative sequence1 – 5252Missing in isoform 3.
VSP_044868
Alternative sequence1441V → VNVSGKFYEYMLKGEISSHE LNNVQDNEMLRKV in isoform 2 and isoform 3.
VSP_042030

Experimental info

Sequence conflict201R → G in AAH35029. Ref.4
Sequence conflict921K → E in BAF82464. Ref.2
Sequence conflict1441V → I in BAH14626. Ref.2
Sequence conflict3071A → T in BAH14626. Ref.2
Sequence conflict3721T → M in BAF82464. Ref.2
Sequence conflict3731E → G in BAG62192. Ref.2
Sequence conflict6341A → S in BAF82464. Ref.2

Sequences

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

Last modified May 1, 1999. Version 2.
Checksum: F6416596229F2639

FASTA66974,162
        10         20         30         40         50         60 
MARRGWRRAP LRRGVGSSPR ARRLMRPLWL LLAVGVFDWA GASDGGGGEA RAMDEEIVSE 

        70         80         90        100        110        120 
KQAEESHRQD SANLLIFILL LTLTILTIWL FKHRRARFLH ETGLAMIYGL LVGLVLRYGI 

       130        140        150        160        170        180 
HVPSDVNNVT LSCEVQSSPT TLLVTFDPEV FFNILLPPII FYAGYSLKRR HFFRNLGSIL 

       190        200        210        220        230        240 
AYAFLGTAIS CFVIGSIMYG CVTLMKVTGQ LAGDFYFTDC LLFGAIVSAT DPVTVLAIFH 

       250        260        270        280        290        300 
ELQVDVELYA LLFGESVLND AVAIVLSSSI VAYQPAGDNS HTFDVTAMFK SIGIFLGIFS 

       310        320        330        340        350        360 
GSFAMGAATG VVTALVTKFT KLREFQLLET GLFFLMSWST FLLAEAWGFT GVVAVLFCGI 

       370        380        390        400        410        420 
TQAHYTYNNL STESQHRTKQ LFELLNFLAE NFIFSYMGLT LFTFQNHVFN PTFVVGAFVA 

       430        440        450        460        470        480 
IFLGRAANIY PLSLLLNLGR RSKIGSNFQH MMMFAGLRGA MAFALAIRDT ATYARQMMFS 

       490        500        510        520        530        540 
TTLLIVFFTV WVFGGGTTAM LSCLHIRVGV DSDQEHLGVP ENERRTTKAE SAWLFRMWYN 

       550        560        570        580        590        600 
FDHNYLKPLL THSGPPLTTT LPACCGPIAR CLTSPQAYEN QEQLKDDDSD LILNDGDISL 

       610        620        630        640        650        660 
TYGDSTVNTE PATSSAPRRF MGNSSEDALD RELAFGDHEL VIRGTRLVLP MDDSEPPLNL 


LDNTRHGPA 

« Hide

Isoform 2 [UniParc].

Checksum: A2BE0E4EF07A62EC
Show »

FASTA70177,917
Isoform 3 [UniParc].

Checksum: F875E7739A25438F
Show »

FASTA64972,260

References

« Hide 'large scale' references
[1]"Identification of a mitochondrial Na+/H+ exchanger."
Numata M., Petrecca K., Lake N., Orlowski J.
J. Biol. Chem. 273:6951-6959(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
Tissue: Brain and Placenta.
[3]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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: Brain.
[5]"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain."
Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N.
DNA Res. 3:321-329(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-669 (ISOFORM 1).
Tissue: Bone marrow.
[6]"Human Na(+)/H(+) exchanger isoform 6 is found in recycling endosomes of cells, not in mitochondria."
Brett C.L., Wei Y., Donowitz M., Rao R.
Am. J. Physiol. 282:C1031-C1041(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]"Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry."
Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.
Proteomics 7:868-874(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-443.
Tissue: Mammary cancer.
[8]"SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome."
Gilfillan G.D., Selmer K.K., Roxrud I., Smith R., Kyllerman M., Eiklid K., Kroken M., Mattingsdal M., Egeland T., Stenmark H., Sjoholm H., Server A., Samuelsson L., Christianson A., Tarpey P., Whibley A., Stratton M.R., Futreal P.A. expand/collapse author list , Teague J., Edkins S., Gecz J., Turner G., Raymond F.L., Schwartz C., Stevenson R.E., Undlien D.E., Stromme P.
Am. J. Hum. Genet. 82:1003-1010(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MRXSCH.
[9]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-128.
Tissue: Liver.
[10]"Identification of pathogenic gene variants in small families with intellectually disabled siblings by exome sequencing."
Schuurs-Hoeijmakers J.H., Vulto-van Silfhout A.T., Vissers L.E., van de Vondervoort I.I., van Bon B.W., de Ligt J., Gilissen C., Hehir-Kwa J.Y., Neveling K., del Rosario M., Hira G., Reitano S., Vitello A., Failla P., Greco D., Fichera M., Galesi O., Kleefstra T. expand/collapse author list , Greally M.T., Ockeloen C.W., Willemsen M.H., Bongers E.M., Janssen I.M., Pfundt R., Veltman J.A., Romano C., Willemsen M.A., van Bokhoven H., Brunner H.G., de Vries B.B., de Brouwer A.P.
J. Med. Genet. 50:802-811(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MRXSCH.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF030409 mRNA. Translation: AAC39643.1.
AK289775 mRNA. Translation: BAF82464.1.
AK300475 mRNA. Translation: BAG62192.1.
AK316255 mRNA. Translation: BAH14626.1.
AL732579 Genomic DNA. Translation: CAI39923.1.
AL732579 Genomic DNA. Translation: CAI39924.1.
AL732579 Genomic DNA. Translation: CAI39925.1.
BC035029 mRNA. Translation: AAH35029.1.
BC049169 mRNA. Translation: AAH49169.1.
D87743 mRNA. Translation: BAA13449.1.
RefSeqNP_001036002.1. NM_001042537.1.
NP_001171122.1. NM_001177651.1.
NP_006350.1. NM_006359.2.
UniGeneHs.62185.

3D structure databases

ProteinModelPortalQ92581.
SMRQ92581. Positions 218-246, 337-364.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115742. 2 interactions.
STRING9606.ENSP00000359729.

Protein family/group databases

TCDB2.A.36.1.14. the monovalent cation:proton antiporter-1 (cpa1) family.

PTM databases

PhosphoSiteQ92581.

Polymorphism databases

DMDM6919937.

Proteomic databases

PaxDbQ92581.
PRIDEQ92581.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000370695; ENSP00000359729; ENSG00000198689. [Q92581-2]
ENST00000370698; ENSP00000359732; ENSG00000198689. [Q92581-1]
ENST00000370701; ENSP00000359735; ENSG00000198689. [Q92581-3]
ENST00000595850; ENSP00000470998; ENSG00000269036. [Q92581-3]
ENST00000595964; ENSP00000471427; ENSG00000269036. [Q92581-2]
ENST00000597470; ENSP00000470918; ENSG00000269036. [Q92581-1]
GeneID10479.
KEGGhsa:10479.
UCSCuc004ezj.3. human. [Q92581-1]
uc004ezk.3. human. [Q92581-2]
uc011mvx.2. human.

Organism-specific databases

CTD10479.
GeneCardsGC0XP135068.
HGNCHGNC:11079. SLC9A6.
HPAHPA059445.
MIM300231. gene.
300243. phenotype.
neXtProtNX_Q92581.
Orphanet85278. Christianson syndrome.
PharmGKBPA35935.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0025.
HOGENOMHOG000172307.
HOVERGENHBG055575.
KOK12041.
OMADQEHLGV.
OrthoDBEOG7NW69D.
PhylomeDBQ92581.
TreeFamTF318755.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ92581.
BgeeQ92581.
CleanExHS_SLC9A6.
GenevestigatorQ92581.

Family and domain databases

InterProIPR006153. Cation/H_exchanger.
IPR018422. Cation/H_exchanger_CPA1.
IPR002090. Na/H_exchanger_6.
IPR004709. NaH_exchanger.
[Graphical view]
PANTHERPTHR10110. PTHR10110. 1 hit.
PfamPF00999. Na_H_Exchanger. 1 hit.
[Graphical view]
PRINTSPR01084. NAHEXCHNGR.
PR01088. NAHEXCHNGR6.
TIGRFAMsTIGR00840. b_cpa1. 1 hit.
ProtoNetSearch...

Other

GeneWikiSLC9A6.
GenomeRNAi10479.
NextBio35480885.
PROQ92581.
SOURCESearch...

Entry information

Entry nameSL9A6_HUMAN
AccessionPrimary (citable) accession number: Q92581
Secondary accession number(s): A6NIQ9 expand/collapse secondary AC list , A8K160, B4DU30, B7ZAE0, Q3ZCW7, Q5JPP8, Q5JPP9, Q86VS0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 131 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

MIM cross-references

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

Human chromosome X

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