Q8IVB4 (SL9A9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium/hydrogen exchanger 9

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

Gene names

Name:	SLC9A9
Synonyms:	NHE9
ORF Names:	Nbla00118

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	645 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May act in electroneutral exchange of protons for Na+ across membranes. Involved in the effusion of Golgi luminal H+ in exchange for cytosolic cations. Involved in organelle ion homeostasis by contributing to the maintenance of the unique acidic pH values of the Golgi and post-Golgi compartments in the cell. Ref.2
Subcellular location	Late endosome membrane; Multi-pass membrane protein Ref.2.
Tissue specificity	Ubiquitously expressed in all tissues tested. Expressed at highest levels in heart and skeletal muscle, followed by placenta, kidney, and liver. Expressed in the brain, in the medulla and spinal cord. Ref.1 Ref.2
Involvement in disease	A chromosomal aberration involving SLC9A9 has been found in a family with early-onset behavioral/developmental disorder with features of attention deficit-hyperactivity disorder and intellectual disability. Inversion inv3(p14:q21). The inversion disrupts DOCK3 and SLC9A9. Autism 16 (AUTS16) [MIM:613410]: A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation. AUTS16 can be associated with epilepsy. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. 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 BAC04005.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Antiport Ion transport Sodium transport Transport
Cellular component	Endosome Membrane
Coding sequence diversity	Chromosomal rearrangement Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ion transport Traceable author statement. Source: Reactome regulation of pH Inferred from electronic annotation. Source: InterPro transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW late endosome membrane Traceable author statement. Source: Reactome recycling endosome Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	sodium:hydrogen antiporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 645	645	Sodium/hydrogen exchanger 9		PRO_0000052367
Regions
	Transmembrane	21 – 41	21	Helical; Potential
	Transmembrane	46 – 66	21	Helical; Potential
	Transmembrane	127 – 147	21	Helical; Potential
	Transmembrane	165 – 185	21	Helical; Potential
	Transmembrane	204 – 224	21	Helical; Potential
	Transmembrane	236 – 256	21	Helical; Potential
	Transmembrane	278 – 298	21	Helical; Potential
	Transmembrane	302 – 322	21	Helical; Potential
	Transmembrane	323 – 343	21	Helical; Potential
	Transmembrane	365 – 385	21	Helical; Potential
	Transmembrane	387 – 407	21	Helical; Potential
	Transmembrane	430 – 450	21	Helical; Potential
	Transmembrane	466 – 486	21	Helical; Potential
Amino acid modifications
	Glycosylation	96	1	N-linked (GlcNAc...) Ref.9
Natural variations
	Natural variant	540	1	I → V. Corresponds to variant rs16853300 [ dbSNP | Ensembl ].		VAR_050232
	Natural variant	589	1	I → V. Ref.3 Corresponds to variant rs2289491 [ dbSNP | Ensembl ].		VAR_022114

Sequences

	Sequence		Length	Mass (Da)
	Q8IVB4 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: E23F7385D0B3ACAB	FASTA	645	72,565
	10 20 30 40 50 60 MERQSRVMSE KDEYQFQHQG AVELLVFNFL LILTILTIWL FKNHRFRFLH ETGGAMVYGL 70 80 90 100 110 120 IMGLILRYAT APTDIESGTV YDCVKLTFSP STLLVNITDQ VYEYKYKREI SQHNINPHQG 130 140 150 160 170 180 NAILEKMTFD PEIFFNVLLP PIIFHAGYSL KKRHFFQNLG SILTYAFLGT AISCIVIGLI 190 200 210 220 230 240 MYGFVKAMIH AGQLKNGDFH FTDCLFFGSL MSATDPVTVL AIFHELHVDP DLYTLLFGES 250 260 270 280 290 300 VLNDAVAIVL TYSISIYSPK ENPNAFDAAA FFQSVGNFLG IFAGSFAMGS AYAIITALLT 310 320 330 340 350 360 KFTKLCEFPM LETGLFFLLS WSAFLSAEAA GLTGIVAVLF CGVTQAHYTY NNLSSDSKIR 370 380 390 400 410 420 TKQLFEFMNF LAENVIFCYM GLALFTFQNH IFNALFILGA FLAIFVARAC NIYPLSFLLN 430 440 450 460 470 480 LGRKQKIPWN FQHMMMFSGL RGAIAFALAI RNTESQPKQM MFTTTLLLVF FTVWVFGGGT 490 500 510 520 530 540 TPMLTWLQIR VGVDLDENLK EDPSSQHQEA NNLDKNMTKA ESARLFRMWY SFDHKYLKPI 550 560 570 580 590 600 LTHSGPPLTT TLPEWCGPIS RLLTSPQAYG EQLKEDDVEC IVNQDELAIN YQEQASSPCS 610 620 630 640 PPARLGLDQK ASPQTPGKEN IYEGDLGLGG YELKLEQTLG QSQLN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Disruption of a novel member of a sodium/hydrogen exchanger family and DOCK3 is associated with an attention deficit hyperactivity disorder-like phenotype." De Silva M.G., Elliott K., Dahl H.-H.M., Fitzpatrick E., Wilcox S., Delatycki M., Williamson R., Efron D., Lynch M., Forrest S. J. Med. Genet. 40:733-740(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, CHROMOSOMAL REARRANGEMENT.
[2]	"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: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]	"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], VARIANT VAL-589. Tissue: Lymph node.
[4]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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]. Tissue: Ovary.
[6]	"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] OF 248-645. Tissue: Spleen.
[7]	"Neuroblastoma oligo-capping cDNA project: toward the understanding of the genesis and biology of neuroblastoma." Ohira M., Morohashi A., Nakamura Y., Isogai E., Furuya K., Hamano S., Machida T., Aoyama M., Fukumura M., Miyazaki K., Suzuki Y., Sugano S., Hirato J., Nakagawara A. Cancer Lett. 197:63-68(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 431-645. Tissue: Neuroblastoma.
[8]	"Identifying autism loci and genes by tracing recent shared ancestry." Morrow E.M., Yoo S.-Y., Flavell S.W., Kim T.-K., Lin Y., Hill R.S., Mukaddes N.M., Balkhy S., Gascon G., Hashmi A., Al-Saad S., Ware J., Joseph R.M., Greenblatt R., Gleason D., Ertelt J.A., Apse K.A., Bodell A. , Partlow J.N., Barry B., Yao H., Markianos K., Ferland R.J., Greenberg M.E., Walsh C.A. Science 321:218-223(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN AUTS16.
[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-96, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY254100 mRNA. Translation: AAP80573.1. AB089794 mRNA. Translation: BAD69592.1. AL832304 mRNA. Translation: CAI46158.1. AC131210 Genomic DNA. No translation available. BC035779 mRNA. Translation: AAH35779.1. AK092932 mRNA. Translation: BAC04005.1. Different initiation. AB075486 mRNA. Translation: BAE45746.1.
IPI	IPI00216972.
RefSeq	NP_775924.1. NM_173653.3.
UniGene	Hs.302257.
3D structure databases
ProteinModelPortal	Q8IVB4.
SMR	Q8IVB4. Positions 202-230.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000320246.
PTM databases
PhosphoSite	Q8IVB4.
Polymorphism databases
DMDM	44888222.
Proteomic databases
PaxDb	Q8IVB4.
PRIDE	Q8IVB4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000316549; ENSP00000320246; ENSG00000181804.
GeneID	285195.
KEGG	hsa:285195.
UCSC	uc003evn.3. human.
Organism-specific databases
CTD	285195.
GeneCards	GC03M142984.
HGNC	HGNC:20653. SLC9A9.
MIM	608396. gene. 613410. phenotype.
neXtProt	NX_Q8IVB4.
PharmGKB	PA134889062.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0025.
HOGENOM	HOG000172307.
HOVERGEN	HBG055575.
InParanoid	Q8IVB4.
KO	K14725.
OMA	PQAYGEQ.
OrthoDB	EOG4NCMCC.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q8IVB4.
Bgee	Q8IVB4.
CleanEx	HS_SLC9A9.
Genevestigator	Q8IVB4.
GermOnline	ENSG00000181804. Homo sapiens.
Family and domain databases
InterPro	IPR006153. Cation/H_exchanger. IPR018422. Cation/H_exchanger_CPA1. IPR002090. Na/H_exchanger_6. IPR004709. NaH_exchanger. [Graphical view]
PANTHER	PTHR10110. PTHR10110. 1 hit.
Pfam	PF00999. Na_H_Exchanger. 1 hit. [Graphical view]
PRINTS	PR01084. NAHEXCHNGR. PR01088. NAHEXCHNGR6.
TIGRFAMs	TIGR00840. b_cpa1. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	285195.
NextBio	95343.
SOURCE	Search...

Entry information

Entry name

SL9A9_HUMAN

Accession

Primary (citable) accession number: Q8IVB4
Secondary accession number(s): A6NMQ9 , Q3LIC2, Q5JPI6, Q5WA58, Q8NAB9

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2004
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 97 of the entry and version 1 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.