Q9Y2E8 (SL9A8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium/hydrogen exchanger 8

Alternative name(s):
Na(+)/H(+) exchanger 8
Short name=NHE-8
Solute carrier family 9 member 8

Gene names

Name:	SLC9A8
Synonyms:	KIAA0939, NHE8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	581 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. Ref.8
Subcellular location	Golgi apparatus membrane; Multi-pass membrane protein Ref.8.
Tissue specificity	Ubiquitous. Strongly expressed in skeletal muscle and kidney. Ref.8
Sequence similarities	Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. [View classification]
Sequence caution	The sequence BAA76783.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Antiport Ion transport Sodium transport Transport
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ion transport Traceable author statement. Source: Reactome regulation of intracellular pH Inferred from electronic annotation. Source: Compara transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	potassium:hydrogen antiporter activity Inferred from electronic annotation. Source: Compara sodium:hydrogen antiporter activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y2E8-1)

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: Q9Y2E8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     178-178: Q → QGFFFVCVCVFVCFILQ

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 581	581	Sodium/hydrogen exchanger 8		PRO_0000052365
Regions
	Transmembrane	60 – 80	21	Helical; Potential
	Transmembrane	84 – 104	21	Helical; Potential
	Transmembrane	123 – 143	21	Helical; Potential
	Transmembrane	156 – 176	21	Helical; Potential
	Transmembrane	191 – 211	21	Helical; Potential
	Transmembrane	264 – 284	21	Helical; Potential
	Transmembrane	311 – 331	21	Helical; Potential
	Transmembrane	354 – 374	21	Helical; Potential
	Transmembrane	379 – 399	21	Helical; Potential
	Transmembrane	417 – 437	21	Helical; Potential
	Transmembrane	451 – 471	21	Helical; Potential
Amino acid modifications
	Modified residue	571	1	Phosphoserine Ref.9
	Modified residue	573	1	Phosphoserine Ref.9
Natural variations
	Alternative sequence	178	1	Q → QGFFFVCVCVFVCFILQ in isoform 2.		VSP_037686
Experimental info
	Sequence conflict	114	1	N → D in BAC85475. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 28, 2009. Version 4. Checksum: 7508B62B74D584B1	FASTA	581	65,422
	10 20 30 40 50 60 MGEKMAEEER FPNTTHEGFN VTLHTTLVVT TKLVLPTPGK PILPVQTGEQ AQQEEQSSGM 70 80 90 100 110 120 TIFFSLLVLA ICIILVHLLI RYRLHFLPES VAVVSLGILM GAVIKIIEFK KLANWKEEEM 130 140 150 160 170 180 FRPNMFFLLL LPPIIFESGY SLHKGNFFQN IGSITLFAVF GTAISAFVVG GGIYFLGQAD 190 200 210 220 230 240 VISKLNMTDS FAFGSLISAV DPVATIAIFN ALHVDPVLNM LVFGESILND AVSIVLTNTA 250 260 270 280 290 300 EGLTRKNMSD VSGWQTFLQA LDYFLKMFFG SAALGTLTGL ISALVLKHID LRKTPSLEFG 310 320 330 340 350 360 MMIIFAYLPY GLAEGISLSG IMAILFSGIV MSHYTHHNLS PVTQILMQQT LRTVAFLCET 370 380 390 400 410 420 CVFAFLGLSI FSFPHKFEIS FVIWCIVLVL FGRAVNIFPL SYLLNFFRDH KITPKMMFIM 430 440 450 460 470 480 WFSGLRGAIP YALSLHLDLE PMEKRQLIGT TTIVIVLFTI LLLGGSTMPL IRLMDIEDAK 490 500 510 520 530 540 AHRRNKKDVN LSKTEKMGNT VESEHLSELT EEEYEAHYIR RQDLKGFVWL DAKYLNPFFT 550 560 570 580 RRLTQEDLHH GRIQMKTLTN KWYEEVRQGP SGSEDDEQEL L
	Isoform 2 [UniParc]. Checksum: F82E64383B1E4192	FASTA	597	67,275
	10 20 30 40 50 60 MGEKMAEEER FPNTTHEGFN VTLHTTLVVT TKLVLPTPGK PILPVQTGEQ AQQEEQSSGM 70 80 90 100 110 120 TIFFSLLVLA ICIILVHLLI RYRLHFLPES VAVVSLGILM GAVIKIIEFK KLANWKEEEM 130 140 150 160 170 180 FRPNMFFLLL LPPIIFESGY SLHKGNFFQN IGSITLFAVF GTAISAFVVG GGIYFLGQGF 190 200 210 220 230 240 FFVCVCVFVC FILQADVISK LNMTDSFAFG SLISAVDPVA TIAIFNALHV DPVLNMLVFG 250 260 270 280 290 300 ESILNDAVSI VLTNTAEGLT RKNMSDVSGW QTFLQALDYF LKMFFGSAAL GTLTGLISAL 310 320 330 340 350 360 VLKHIDLRKT PSLEFGMMII FAYLPYGLAE GISLSGIMAI LFSGIVMSHY THHNLSPVTQ 370 380 390 400 410 420 ILMQQTLRTV AFLCETCVFA FLGLSIFSFP HKFEISFVIW CIVLVLFGRA VNIFPLSYLL 430 440 450 460 470 480 NFFRDHKITP KMMFIMWFSG LRGAIPYALS LHLDLEPMEK RQLIGTTTIV IVLFTILLLG 490 500 510 520 530 540 GSTMPLIRLM DIEDAKAHRR NKKDVNLSKT EKMGNTVESE HLSELTEEEY EAHYIRRQDL 550 560 570 580 590 KGFVWLDAKY LNPFFTRRLT QEDLHHGRIQ MKTLTNKWYE EVRQGPSGSE DDEQELL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:63-70(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[3]	"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. , 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] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-155 (ISOFORM 1). Tissue: Gastric mucosa and Placenta.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Small intestine.
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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. , 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].
[7]	"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 1).
[8]	"Four Na+/H+ exchanger isoforms are distributed to Golgi and post-Golgi Compartments and are involved in organelle pH regulation." Nakamura N., Tanaka S., Teko Y., Mitsui K., Kanazawa H. J. Biol. Chem. 280:1561-1572(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"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-571 AND SER-573, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB023156 mRNA. Translation: BAA76783.2. Different initiation. AK131001 mRNA. Translation: BAC85475.1. Different termination. AK300318 mRNA. Translation: BAG62070.1. CR749638 mRNA. Translation: CAH18432.1. AL162615, AL031685 Genomic DNA. Translation: CAI18970.1. AL031685, AL162615 Genomic DNA. Translation: CAI23460.1. CH471077 Genomic DNA. Translation: EAW75649.1. BC112213 mRNA. Translation: AAI12214.1.
IPI	IPI00183933. IPI00943142.
RefSeq	NP_001247420.1. NM_001260491.1. NP_056081.1. NM_015266.2.
UniGene	Hs.444202.
3D structure databases
ProteinModelPortal	Q9Y2E8.
SMR	Q9Y2E8. Positions 188-216.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y2E8. 1 interaction.
STRING	9606.ENSP00000354966.
Protein family/group databases
TCDB	2.A.36.1.9. monovalent cation:proton antiporter-1 (CPA1) family.
PTM databases
PhosphoSite	Q9Y2E8.
Polymorphism databases
DMDM	254763448.
Proteomic databases
PaxDb	Q9Y2E8.
PRIDE	Q9Y2E8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000361573; ENSP00000354966; ENSG00000197818. ENST00000417961; ENSP00000416418; ENSG00000197818.
GeneID	23315.
KEGG	hsa:23315.
UCSC	uc002xuv.1. human. uc010zyj.1. human.
Organism-specific databases
CTD	23315.
GeneCards	GC20P048429.
HGNC	HGNC:20728. SLC9A8.
HPA	CAB033682.
MIM	612730. gene.
neXtProt	NX_Q9Y2E8.
PharmGKB	PA134924114.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0025.
HOGENOM	HOG000172307.
HOVERGEN	HBG056815.
InParanoid	Q9Y2E8.
KO	K14724.
OMA	IKLSGIM.
OrthoDB	EOG43BMNS.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q9Y2E8.
Bgee	Q9Y2E8.
CleanEx	HS_SLC9A8.
Genevestigator	Q9Y2E8.
GermOnline	ENSG00000197818. Homo sapiens.
Family and domain databases
InterPro	IPR006153. Cation/H_exchanger. IPR018422. Cation/H_exchanger_CPA1. IPR018409. Na/H_exchanger_8_eu. IPR004709. NaH_exchanger. [Graphical view]
PANTHER	PTHR10110. PTHR10110. 1 hit. PTHR10110:SF9. PTHR10110:SF9. 1 hit.
Pfam	PF00999. Na_H_Exchanger. 1 hit. [Graphical view]
PRINTS	PR01084. NAHEXCHNGR.
TIGRFAMs	TIGR00840. b_cpa1. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	SLC9A8. human.
GenomeRNAi	23315.
NextBio	45196.
SOURCE	Search...

Entry information

Entry name

SL9A8_HUMAN

Accession

Primary (citable) accession number: Q9Y2E8
Secondary accession number(s): B4DTQ8 , Q2M1U9, Q68CZ8, Q9BX15, Q9Y507

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	July 28, 2009
Last modified:	April 3, 2013
This is version 106 of the entry and version 4 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.