SL9A9_HUMAN
ID SL9A9_HUMAN Reviewed; 645 AA.
AC Q8IVB4; A6NMQ9; Q3LIC2; Q5JPI6; Q5WA58; Q8NAB9;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Sodium/hydrogen exchanger 9;
DE AltName: Full=Na(+)/H(+) exchanger 9;
DE Short=NHE-9;
DE AltName: Full=Solute carrier family 9 member 9;
GN Name=SLC9A9; Synonyms=NHE9; ORFNames=Nbla00118;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND CHROMOSOMAL
RP REARRANGEMENT.
RX PubMed=14569117; DOI=10.1136/jmg.40.10.733;
RA De Silva M.G., Elliott K., Dahl H.-H.M., Fitzpatrick E., Wilcox S.,
RA Delatycki M., Williamson R., Efron D., Lynch M., Forrest S.;
RT "Disruption of a novel member of a sodium/hydrogen exchanger family and
RT DOCK3 is associated with an attention deficit hyperactivity disorder-like
RT phenotype.";
RL J. Med. Genet. 40:733-740(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=15522866; DOI=10.1074/jbc.m410041200;
RA Nakamura N., Tanaka S., Teko Y., Mitsui K., Kanazawa H.;
RT "Four Na+/H+ exchanger isoforms are distributed to Golgi and post-Golgi
RT Compartments and are involved in organelle pH regulation.";
RL J. Biol. Chem. 280:1561-1572(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-589.
RC TISSUE=Lymph node;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 248-645.
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 431-645.
RC TISSUE=Neuroblastoma;
RX PubMed=12880961; DOI=10.1016/s0304-3835(03)00085-5;
RA Ohira M., Morohashi A., Nakamura Y., Isogai E., Furuya K., Hamano S.,
RA Machida T., Aoyama M., Fukumura M., Miyazaki K., Suzuki Y., Sugano S.,
RA Hirato J., Nakagawara A.;
RT "Neuroblastoma oligo-capping cDNA project: toward the understanding of the
RT genesis and biology of neuroblastoma.";
RL Cancer Lett. 197:63-68(2003).
RN [8]
RP INVOLVEMENT IN AUTS16.
RX PubMed=18621663; DOI=10.1126/science.1157657;
RA Morrow E.M., Yoo S.-Y., Flavell S.W., Kim T.-K., Lin Y., Hill R.S.,
RA Mukaddes N.M., Balkhy S., Gascon G., Hashmi A., Al-Saad S., Ware J.,
RA Joseph R.M., Greenblatt R., Gleason D., Ertelt J.A., Apse K.A., Bodell A.,
RA Partlow J.N., Barry B., Yao H., Markianos K., Ferland R.J., Greenberg M.E.,
RA Walsh C.A.;
RT "Identifying autism loci and genes by tracing recent shared ancestry.";
RL Science 321:218-223(2008).
RN [9]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-96.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: May act in electroneutral exchange of protons for Na(+)
CC across membranes. Involved in the effusion of Golgi luminal H(+) in
CC exchange for cytosolic cations. Involved in organelle ion homeostasis
CC by contributing to the maintenance of the unique acidic pH values of
CC the Golgi and post-Golgi compartments in the cell.
CC {ECO:0000269|PubMed:15522866}.
CC -!- INTERACTION:
CC Q8IVB4; Q8IUH5: ZDHHC17; NbExp=2; IntAct=EBI-9092184, EBI-524753;
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000269|PubMed:15522866}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15522866}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissues tested.
CC Expressed at highest levels in heart and skeletal muscle, followed by
CC placenta, kidney, and liver. Expressed in the brain, in the medulla and
CC spinal cord. {ECO:0000269|PubMed:14569117,
CC ECO:0000269|PubMed:15522866}.
CC -!- DISEASE: Note=A chromosomal aberration involving SLC9A9 has been found
CC in a family with early-onset behavioral/developmental disorder with
CC features of attention deficit-hyperactivity disorder and intellectual
CC disability. Inversion inv(3)(p14:q21). The inversion disrupts DOCK3 and
CC SLC9A9.
CC -!- DISEASE: Autism 16 (AUTS16) [MIM:613410]: A complex multifactorial,
CC pervasive developmental disorder characterized by impairments in
CC reciprocal social interaction and communication, restricted and
CC stereotyped patterns of interests and activities, and the presence of
CC developmental abnormalities by 3 years of age. Most individuals with
CC autism also manifest moderate intellectual disability. AUTS16 can be
CC associated with epilepsy. {ECO:0000269|PubMed:18621663}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1)
CC transporter (TC 2.A.36) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC04005.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY254100; AAP80573.1; -; mRNA.
DR EMBL; AB089794; BAD69592.1; -; mRNA.
DR EMBL; AL832304; CAI46158.1; -; mRNA.
DR EMBL; AC131210; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035779; AAH35779.1; -; mRNA.
DR EMBL; AK092932; BAC04005.1; ALT_INIT; mRNA.
DR EMBL; AB075486; BAE45746.1; -; mRNA.
DR CCDS; CCDS33872.1; -.
DR RefSeq; NP_775924.1; NM_173653.3.
DR AlphaFoldDB; Q8IVB4; -.
DR SMR; Q8IVB4; -.
DR BioGRID; 130044; 3.
DR IntAct; Q8IVB4; 3.
DR MINT; Q8IVB4; -.
DR STRING; 9606.ENSP00000320246; -.
DR TCDB; 2.A.36.1.19; the monovalent cation:proton antiporter-1 (cpa1) family.
DR GlyGen; Q8IVB4; 1 site.
DR iPTMnet; Q8IVB4; -.
DR PhosphoSitePlus; Q8IVB4; -.
DR SwissPalm; Q8IVB4; -.
DR BioMuta; SLC9A9; -.
DR DMDM; 44888222; -.
DR EPD; Q8IVB4; -.
DR jPOST; Q8IVB4; -.
DR MassIVE; Q8IVB4; -.
DR PaxDb; Q8IVB4; -.
DR PeptideAtlas; Q8IVB4; -.
DR PRIDE; Q8IVB4; -.
DR ProteomicsDB; 70678; -.
DR Antibodypedia; 18118; 218 antibodies from 27 providers.
DR DNASU; 285195; -.
DR Ensembl; ENST00000316549.11; ENSP00000320246.6; ENSG00000181804.15.
DR GeneID; 285195; -.
DR KEGG; hsa:285195; -.
DR MANE-Select; ENST00000316549.11; ENSP00000320246.6; NM_173653.4; NP_775924.1.
DR UCSC; uc003evn.3; human.
DR CTD; 285195; -.
DR DisGeNET; 285195; -.
DR GeneCards; SLC9A9; -.
DR HGNC; HGNC:20653; SLC9A9.
DR HPA; ENSG00000181804; Low tissue specificity.
DR MalaCards; SLC9A9; -.
DR MIM; 608396; gene.
DR MIM; 613410; phenotype.
DR neXtProt; NX_Q8IVB4; -.
DR OpenTargets; ENSG00000181804; -.
DR Orphanet; 106; NON RARE IN EUROPE: Autism.
DR PharmGKB; PA134889062; -.
DR VEuPathDB; HostDB:ENSG00000181804; -.
DR eggNOG; KOG1965; Eukaryota.
DR GeneTree; ENSGT00940000160094; -.
DR HOGENOM; CLU_005912_7_0_1; -.
DR InParanoid; Q8IVB4; -.
DR OMA; IHETVIS; -.
DR OrthoDB; 559433at2759; -.
DR PhylomeDB; Q8IVB4; -.
DR TreeFam; TF318755; -.
DR PathwayCommons; Q8IVB4; -.
DR Reactome; R-HSA-425986; Sodium/Proton exchangers.
DR Reactome; R-HSA-5619052; Defective SLC9A9 causes autism 16 (AUTS16).
DR SignaLink; Q8IVB4; -.
DR SIGNOR; Q8IVB4; -.
DR BioGRID-ORCS; 285195; 9 hits in 1071 CRISPR screens.
DR ChiTaRS; SLC9A9; human.
DR GenomeRNAi; 285195; -.
DR Pharos; Q8IVB4; Tbio.
DR PRO; PR:Q8IVB4; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8IVB4; protein.
DR Bgee; ENSG00000181804; Expressed in calcaneal tendon and 171 other tissues.
DR ExpressionAtlas; Q8IVB4; baseline and differential.
DR Genevisible; Q8IVB4; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031902; C:late endosome membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0015386; F:potassium:proton antiporter activity; IBA:GO_Central.
DR GO; GO:0015385; F:sodium:proton antiporter activity; IBA:GO_Central.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0051453; P:regulation of intracellular pH; IBA:GO_Central.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; IBA:GO_Central.
DR InterPro; IPR006153; Cation/H_exchanger.
DR InterPro; IPR018422; Cation/H_exchanger_CPA1.
DR InterPro; IPR018416; Na/H_exchanger_9.
DR InterPro; IPR004709; NaH_exchanger.
DR InterPro; IPR002090; NHE-6/7/9.
DR PANTHER; PTHR10110; PTHR10110; 1.
DR PANTHER; PTHR10110:SF61; PTHR10110:SF61; 1.
DR Pfam; PF00999; Na_H_Exchanger; 1.
DR PRINTS; PR01084; NAHEXCHNGR.
DR PRINTS; PR01088; NAHEXCHNGR6.
DR TIGRFAMs; TIGR00840; b_cpa1; 1.
PE 1: Evidence at protein level;
KW Antiport; Autism; Autism spectrum disorder; Chromosomal rearrangement;
KW Endosome; Glycoprotein; Ion transport; Membrane; Reference proteome;
KW Sodium; Sodium transport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..645
FT /note="Sodium/hydrogen exchanger 9"
FT /id="PRO_0000052367"
FT TRANSMEM 21..41
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 46..66
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..147
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 165..185
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 236..256
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 278..298
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 302..322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 323..343
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 365..385
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 387..407
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 430..450
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 466..486
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 594..622
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VARIANT 540
FT /note="I -> V (in dbSNP:rs16853300)"
FT /id="VAR_050232"
FT VARIANT 589
FT /note="I -> V (in dbSNP:rs2289491)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_022114"
SQ SEQUENCE 645 AA; 72565 MW; E23F7385D0B3ACAB CRC64;
MERQSRVMSE KDEYQFQHQG AVELLVFNFL LILTILTIWL FKNHRFRFLH ETGGAMVYGL
IMGLILRYAT APTDIESGTV YDCVKLTFSP STLLVNITDQ VYEYKYKREI SQHNINPHQG
NAILEKMTFD PEIFFNVLLP PIIFHAGYSL KKRHFFQNLG SILTYAFLGT AISCIVIGLI
MYGFVKAMIH AGQLKNGDFH FTDCLFFGSL MSATDPVTVL AIFHELHVDP DLYTLLFGES
VLNDAVAIVL TYSISIYSPK ENPNAFDAAA FFQSVGNFLG IFAGSFAMGS AYAIITALLT
KFTKLCEFPM LETGLFFLLS WSAFLSAEAA GLTGIVAVLF CGVTQAHYTY NNLSSDSKIR
TKQLFEFMNF LAENVIFCYM GLALFTFQNH IFNALFILGA FLAIFVARAC NIYPLSFLLN
LGRKQKIPWN FQHMMMFSGL RGAIAFALAI RNTESQPKQM MFTTTLLLVF FTVWVFGGGT
TPMLTWLQIR VGVDLDENLK EDPSSQHQEA NNLDKNMTKA ESARLFRMWY SFDHKYLKPI
LTHSGPPLTT TLPEWCGPIS RLLTSPQAYG EQLKEDDVEC IVNQDELAIN YQEQASSPCS
PPARLGLDQK ASPQTPGKEN IYEGDLGLGG YELKLEQTLG QSQLN
