SL9A7_HUMAN
ID SL9A7_HUMAN Reviewed; 725 AA.
AC Q96T83; O75827; Q5JXP9;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Sodium/hydrogen exchanger 7;
DE AltName: Full=Na(+)/H(+) exchanger 7;
DE Short=NHE-7;
DE AltName: Full=Solute carrier family 9 member 7;
GN Name=SLC9A7; Synonyms=NHE7;
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], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11279194; DOI=10.1074/jbc.m101319200;
RA Numata M., Orlowski J.;
RT "Molecular cloning and characterization of a novel (Na+,K+)/H+ exchanger
RT localized to the trans-Golgi network.";
RL J. Biol. Chem. 276:17387-17394(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SCAMP1; SCAMP2 AND SCAMP5.
RX PubMed=15840657; DOI=10.1242/jcs.02315;
RA Lin P.J., Williams W.P., Luu Y., Molday R.S., Orlowski J., Numata M.;
RT "Secretory carrier membrane proteins interact and regulate trafficking of
RT the organellar (Na+,K+)/H+ exchanger NHE7.";
RL J. Cell Sci. 118:1885-1897(2005).
RN [4]
RP INVOLVEMENT IN MRX108, VARIANT MRX108 PHE-515, CHARACTERIZATION OF VARIANT
RP MRX108 PHE-515, FUNCTION, GLYCOSYLATION AT ASN-145, SUBCELLULAR LOCATION,
RP AND TOPOLOGY.
RX PubMed=30335141; DOI=10.1093/hmg/ddy371;
RA Khayat W., Hackett A., Shaw M., Ilie A., Dudding-Byth T., Kalscheuer V.M.,
RA Christie L., Corbett M.A., Juusola J., Friend K.L., Kirmse B.M., Gecz J.,
RA Field M., Orlowski J.;
RT "A recurrent missense variant in SLC9A7 causes nonsyndromic X-linked
RT intellectual disability with alteration of Golgi acidification and aberrant
RT glycosylation.";
RL Hum. Mol. Genet. 28:598-614(2019).
CC -!- FUNCTION: Mediates electroneutral exchange of protons for Na(+) and
CC K(+) across endomembranes. May contribute to the regulation of Golgi
CC apparatus volume and pH. {ECO:0000269|PubMed:11279194,
CC ECO:0000269|PubMed:30335141}.
CC -!- SUBUNIT: Interacts with SCAMP1, SCAMP2 and SCAMP5; may participate in
CC its shuttling from trans-Golgi network to recycling endosomes.
CC {ECO:0000269|PubMed:15840657}.
CC -!- INTERACTION:
CC Q96T83; O15127: SCAMP2; NbExp=9; IntAct=EBI-4319546, EBI-712703;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:15840657, ECO:0000269|PubMed:30335141}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:15840657}. Recycling endosome
CC membrane {ECO:0000269|PubMed:15840657}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:15840657}. Cell membrane
CC {ECO:0000269|PubMed:30335141}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:11279194}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:30335141}.
CC -!- DISEASE: Intellectual developmental disorder, X-linked 108 (MRX108)
CC [MIM:301024]: A form of intellectual disability, a disorder
CC characterized by significantly below average general intellectual
CC functioning associated with impairments in adaptive behavior and
CC manifested during the developmental period. Intellectual deficiency is
CC the only primary symptom of non-syndromic X-linked forms, while
CC syndromic forms present with associated physical, neurological and/or
CC psychiatric manifestations. {ECO:0000269|PubMed:30335141}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: Is not inhibited by amiloride but by benzamil and
CC quinine.
CC -!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1)
CC transporter (TC 2.A.36) family. {ECO:0000305}.
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DR EMBL; AF298591; AAK54508.1; -; mRNA.
DR EMBL; AL050307; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL022165; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS14269.1; -.
DR RefSeq; NP_115980.1; NM_032591.2.
DR AlphaFoldDB; Q96T83; -.
DR SMR; Q96T83; -.
DR BioGRID; 124198; 5.
DR IntAct; Q96T83; 9.
DR MINT; Q96T83; -.
DR STRING; 9606.ENSP00000480916; -.
DR TCDB; 2.A.36.1.3; the monovalent cation:proton antiporter-1 (cpa1) family.
DR GlyGen; Q96T83; 1 site.
DR iPTMnet; Q96T83; -.
DR PhosphoSitePlus; Q96T83; -.
DR SwissPalm; Q96T83; -.
DR BioMuta; SLC9A7; -.
DR DMDM; 44888236; -.
DR EPD; Q96T83; -.
DR jPOST; Q96T83; -.
DR MassIVE; Q96T83; -.
DR MaxQB; Q96T83; -.
DR PaxDb; Q96T83; -.
DR PeptideAtlas; Q96T83; -.
DR PRIDE; Q96T83; -.
DR ProteomicsDB; 78214; -.
DR TopDownProteomics; Q96T83; -.
DR Antibodypedia; 25223; 122 antibodies from 24 providers.
DR DNASU; 84679; -.
DR Ensembl; ENST00000328306.4; ENSP00000330320.4; ENSG00000065923.10.
DR GeneID; 84679; -.
DR KEGG; hsa:84679; -.
DR UCSC; uc004dgu.3; human.
DR CTD; 84679; -.
DR DisGeNET; 84679; -.
DR GeneCards; SLC9A7; -.
DR HGNC; HGNC:17123; SLC9A7.
DR HPA; ENSG00000065923; Tissue enriched (brain).
DR MalaCards; SLC9A7; -.
DR MIM; 300368; gene.
DR MIM; 301024; phenotype.
DR neXtProt; NX_Q96T83; -.
DR OpenTargets; ENSG00000065923; -.
DR Orphanet; 777; X-linked non-syndromic intellectual disability.
DR PharmGKB; PA38200; -.
DR VEuPathDB; HostDB:ENSG00000065923; -.
DR eggNOG; KOG1965; Eukaryota.
DR GeneTree; ENSGT00940000153460; -.
DR InParanoid; Q96T83; -.
DR PhylomeDB; Q96T83; -.
DR TreeFam; TF318755; -.
DR PathwayCommons; Q96T83; -.
DR Reactome; R-HSA-425986; Sodium/Proton exchangers.
DR SignaLink; Q96T83; -.
DR SIGNOR; Q96T83; -.
DR BioGRID-ORCS; 84679; 8 hits in 698 CRISPR screens.
DR ChiTaRS; SLC9A7; human.
DR GenomeRNAi; 84679; -.
DR Pharos; Q96T83; Tbio.
DR PRO; PR:Q96T83; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q96T83; protein.
DR Bgee; ENSG00000065923; Expressed in pons and 173 other tissues.
DR ExpressionAtlas; Q96T83; baseline and differential.
DR Genevisible; Q96T83; HS.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IBA:GO_Central.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0015386; F:potassium:proton antiporter activity; IDA:UniProtKB.
DR GO; GO:0015385; F:sodium:proton antiporter activity; IDA:UniProtKB.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:1905526; P:regulation of Golgi lumen acidification; IMP:UniProtKB.
DR GO; GO:0051453; P:regulation of intracellular pH; IBA:GO_Central.
DR GO; GO:0006885; P:regulation of pH; IDA:UniProtKB.
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; IPR004709; NaH_exchanger.
DR InterPro; IPR002090; NHE-6/7/9.
DR PANTHER; PTHR10110; PTHR10110; 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; Cell membrane; Disease variant; Endosome; Glycoprotein;
KW Golgi apparatus; Intellectual disability; Ion transport; Membrane;
KW Phosphoprotein; Potassium; Potassium transport; Reference proteome; Sodium;
KW Sodium transport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..725
FT /note="Sodium/hydrogen exchanger 7"
FT /id="PRO_0000052363"
FT TOPO_DOM 1..21
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 43..70
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 71..91
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 92..95
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 96..116
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 117..175
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 197..210
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 211..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 232..251
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 252..272
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 273..277
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 278..298
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 299..322
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 323..343
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 344..349
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 350..370
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 371..391
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 392..414
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 415..435
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 436..442
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 443..463
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 464..474
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 475..497
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 498..513
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:30335141"
FT TRANSMEM 514..534
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 535..725
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30335141"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 567..590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 669..714
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 669..689
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 690..707
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 545
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BLV3"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30335141"
FT VARIANT 515
FT /note="L -> F (in MRX108; probable gain-of-function
FT variant; affects the regulation of trans-Golgi network/
FT post-Golgi pH homeostasis, causing alkalinization of these
FT compartments compared to wild-type, hence affecting its own
FT glycosylation and that of exported cargo proteins; no
FT effect on subcellular location in the Golgi apparatus and
FT plasma membrane)"
FT /evidence="ECO:0000269|PubMed:30335141"
FT /id="VAR_082101"
SQ SEQUENCE 725 AA; 80131 MW; 14E50B197863E38F CRC64;
MEPGDAARPG SGRATGAPPP RLLLLPLLLG WGLRVAAAAS ASSSGAAAED SSAMEELATE
KEAEESHRQD SVSLLTFILL LTLTILTIWL FKHRRVRFLH ETGLAMIYGL IVGVILRYGT
PATSGRDKSL SCTQEDRAFS TLLVNVSGKF FEYTLKGEIS PGKINSVEQN DMLRKVTFDP
EVFFNILLPP IIFHAGYSLK KRHFFRNLGS ILAYAFLGTA VSCFIIGNLM YGVVKLMKIM
GQLSDKFYYT DCLFFGAIIS ATDPVTVLAI FNELHADVDL YALLFGESVL NDAVAIVLSS
SIVAYQPAGL NTHAFDAAAF FKSVGIFLGI FSGSFTMGAV TGVNANVTKF TKLHCFPLLE
TALFFLMSWS TFLLAEACGF TGVVAVLFCG ITQAHYTYNN LSVESRSRTK QLFEVLHFLA
ENFIFSYMGL ALFTFQKHVF SPIFIIGAFV AIFLGRAAHI YPLSFFLNLG RRHKIGWNFQ
HMMMFSGLRG AMAFALAIRD TASYARQMMF TTTLLIVFFT VWIIGGGTTP MLSWLNIRVG
VEEPSEEDQN EHHWQYFRVG VDPDQDPPPN NDSFQVLQGD GPDSARGNRT KQESAWIFRL
WYSFDHNYLK PILTHSGPPL TTTLPAWCGL LARCLTSPQV YDNQEPLREE DSDFILTEGD
LTLTYGDSTV TANGSSSSHT ASTSLEGSRR TKSSSEEVLE RDLGMGDQKV SSRGTRLVFP
LEDNA
