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2.A.36.1.14
Sodium/hydrogen exchanger 6 (Na+/H+ exchanger 6) (NHE-6) (Solute carrier family 9 member 6).  This Na+/H+ exchanger is encoded by an X-linked gene that is widely expressed and especially abundant in brain, heart and skeletal muscle where it is implicated in endosomal pH homeostasis and trafficking as well as maintenance of cell polarity. Several mutations in the coding region of NHE6 are linked with severe intellectual disability, autistic behavior, ataxia and other abnormalities (Ilie et al. 2014).  A christianson syndrome-linked mutation disrupts endosomal function and elicits neurodegeneration and cell death (Ilie et al. 2016).  Heterozygous female mice suffer from visuospatial memory and motor coordination deficits similar to but less severe than those observed in X-chromosome hemizygous mutant males (Sikora et al. 2016).

Accession Number:Q92581
Protein Name:Sodium/hydrogen exchanger 6
Length:669
Molecular Weight:74162.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:13
Location1 / Topology2 / Orientation3: Endosome membrane1 / Multi-pass membrane protein2
Substrate Na+, H+

Cross database links:

Genevestigator: Q92581
eggNOG: COG0025
HEGENOM: HOG000172307
Entrez Gene ID: 10479   
Pfam: PF00999   
KEGG: hsa:10479   

Gene Ontology

GO:0031901 C:early endosome membrane
GO:0005789 C:endoplasmic reticulum membrane
GO:0016021 C:integral to membrane
GO:0005792 C:microsome
GO:0005886 C:plasma membrane
GO:0055038 C:recycling endosome membrane
GO:0015385 F:sodium:hydrogen antiporter activity
GO:0006885 P:regulation of pH

References (10)

[1] “Identification of a mitochondrial Na+/H+ exchanger.”  Numata M.et.al.   9507001
[2] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[3] “The DNA sequence of the human X chromosome.”  Ross M.T.et.al.   15772651
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[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.et.al.   9039502
[6] “Human Na(+)/H(+) exchanger isoform 6 is found in recycling endosomes of cells, not in mitochondria.”  Brett C.L.et.al.   11940519
[7] “Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry.”  Denis N.J.et.al.   17370265
[8] “SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and ataxia, a phenotype mimicking Angelman syndrome.”  Gilfillan G.D.et.al.   18342287
[9] “Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.”  Chen R.et.al.   19159218
[10] “Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.”  Mayya V.et.al.   19690332

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MARRGWRRAP LRRGVGSSPR ARRLMRPLWL LLAVGVFDWA GASDGGGGEA RAMDEEIVSE 
61:	KQAEESHRQD SANLLIFILL LTLTILTIWL FKHRRARFLH ETGLAMIYGL LVGLVLRYGI 
121:	HVPSDVNNVT LSCEVQSSPT TLLVTFDPEV FFNILLPPII FYAGYSLKRR HFFRNLGSIL 
181:	AYAFLGTAIS CFVIGSIMYG CVTLMKVTGQ LAGDFYFTDC LLFGAIVSAT DPVTVLAIFH 
241:	ELQVDVELYA LLFGESVLND AVAIVLSSSI VAYQPAGDNS HTFDVTAMFK SIGIFLGIFS 
301:	GSFAMGAATG VVTALVTKFT KLREFQLLET GLFFLMSWST FLLAEAWGFT GVVAVLFCGI 
361:	TQAHYTYNNL STESQHRTKQ LFELLNFLAE NFIFSYMGLT LFTFQNHVFN PTFVVGAFVA 
421:	IFLGRAANIY PLSLLLNLGR RSKIGSNFQH MMMFAGLRGA MAFALAIRDT ATYARQMMFS 
481:	TTLLIVFFTV WVFGGGTTAM LSCLHIRVGV DSDQEHLGVP ENERRTTKAE SAWLFRMWYN 
541:	FDHNYLKPLL THSGPPLTTT LPACCGPIAR CLTSPQAYEN QEQLKDDDSD LILNDGDISL 
601:	TYGDSTVNTE PATSSAPRRF MGNSSEDALD RELAFGDHEL VIRGTRLVLP MDDSEPPLNL 
661:	LDNTRHGPA