SL9A1_HUMAN
ID SL9A1_HUMAN Reviewed; 815 AA.
AC P19634; B1ALD6; D3DPL4; Q96EM2;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 2.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Sodium/hydrogen exchanger 1;
DE AltName: Full=APNH;
DE AltName: Full=Na(+)/H(+) antiporter, amiloride-sensitive;
DE AltName: Full=Na(+)/H(+) exchanger 1;
DE Short=NHE-1;
DE AltName: Full=Solute carrier family 9 member 1;
GN Name=SLC9A1; Synonyms=APNH1, NHE1;
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].
RC TISSUE=Kidney;
RX PubMed=2536298; DOI=10.1016/0092-8674(89)90901-x;
RA Sardet C., Franchi A., Pouyssegur J.;
RT "Molecular cloning, primary structure, and expression of the human growth
RT factor-activatable Na+/H+ antiporter.";
RL Cell 56:271-280(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=2154036; DOI=10.1126/science.2154036;
RA Sardet C., Counillon L., Franchi A., Pouyssegur J.;
RT "Growth factors induce phosphorylation of the Na+/H+ antiporter,
RT glycoprotein of 110 kD.";
RL Science 247:723-726(1990).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=1712287; DOI=10.1002/j.1460-2075.1991.tb07725.x;
RA Tse C.-M., Ma A.I., Yang V.W., Watson A.J.M., Levine S., Montrose M.H.,
RA Potter J., Sardet C., Pouyssegur J., Donowitz M.;
RT "Molecular cloning and expression of a cDNA encoding the rabbit ileal
RT villus cell basolateral membrane Na+/H+ exchanger.";
RL EMBO J. 10:1957-1967(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=8283968; DOI=10.1007/bf00936442;
RA Fliegel L., Dyck J.R., Wang H., Fong C., Haworth R.S.;
RT "Cloning and analysis of the human myocardial Na+/H+ exchanger.";
RL Mol. Cell. Biochem. 125:137-143(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10913675; DOI=10.1016/s0165-4608(99)00246-0;
RA Garden O.A., Musk P., Worthington-White D.A., Dewey M.J., Rich I.N.;
RT "Silent polymorphisms within the coding region of human sodium/hydrogen
RT exchanger isoform-1 cDNA in peripheral blood mononuclear cells of leukemia
RT patients: a comparison with healthy controls.";
RL Cancer Genet. Cytogenet. 120:37-43(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [9]
RP GLYCOSYLATION AT ASN-75, AND O-LINKED GLYCOSYLATION.
RX PubMed=8068684; DOI=10.1021/bi00200a030;
RA Counillon L., Pouyssegur J., Reithmeier R.A.;
RT "The Na+/H+ exchanger NHE-1 possesses N- and O-linked glycosylation
RT restricted to the first N-terminal extracellular domain.";
RL Biochemistry 33:10463-10469(1994).
RN [10]
RP INTERACTION WITH CHP1.
RX PubMed=8967452; DOI=10.1152/ajpcell.1996.270.5.c1493;
RA Goss G., Orlowski J., Grinstein S.;
RT "Coimmunoprecipitation of a 24-kDa protein with NHE1, the ubiquitous
RT isoform of the Na+/H+ exchanger.";
RL Am. J. Physiol. 270:C1493-C1502(1996).
RN [11]
RP FUNCTION IN PH REGULATION, AND INTERACTION WITH CHP1.
RX PubMed=8901634; DOI=10.1073/pnas.93.22.12631;
RA Lin X., Barber D.L.;
RT "A calcineurin homologous protein inhibits GTPase-stimulated Na-H
RT exchange.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:12631-12636(1996).
RN [12]
RP TOPOLOGY.
RX PubMed=9688597; DOI=10.1152/ajpcell.1998.275.2.c431;
RA Shrode L.D., Gan B.S., D'Souza S.J., Orlowski J., Grinstein S.;
RT "Topological analysis of NHE1, the ubiquitous Na+/H+ exchanger using
RT chymotryptic cleavage.";
RL Am. J. Physiol. 275:C431-C439(1998).
RN [13]
RP TOPOLOGY, AND MUTAGENESIS OF ARG-180 AND GLN-181.
RX PubMed=10713111; DOI=10.1074/jbc.275.11.7942;
RA Wakabayashi S., Pang T., Su X., Shigekawa M.;
RT "A novel topology model of the human Na(+)/H(+) exchanger isoform 1.";
RL J. Biol. Chem. 275:7942-7949(2000).
RN [14]
RP INTERACTION WITH TESC, AND SUBCELLULAR LOCATION.
RX PubMed=11696366; DOI=10.1016/s0014-5793(01)02986-6;
RA Mailaender J., Mueller-Esterl W., Dedio J.;
RT "Human homolog of mouse tescalcin associates with Na(+)/H(+) exchanger
RT type-1.";
RL FEBS Lett. 507:331-335(2001).
RN [15]
RP FUNCTION, INTERACTION WITH CHP1, AND MUTAGENESIS OF ILE-518; ILE-522;
RP PHE-526; LEU-527; LEU-530; LEU-531 AND 526-PHE--LEU-531.
RX PubMed=11350981; DOI=10.1074/jbc.m100296200;
RA Pang T., Su X., Wakabayashi S., Shigekawa M.;
RT "Calcineurin homologous protein as an essential cofactor for Na+/H+
RT exchangers.";
RL J. Biol. Chem. 276:17367-17372(2001).
RN [16]
RP INTERACTION WITH CHP2.
RX PubMed=12226101; DOI=10.1074/jbc.m208313200;
RA Pang T., Wakabayashi S., Shigekawa M.;
RT "Expression of calcineurin B homologous protein 2 protects serum
RT deprivation-induced cell death by serum-independent activation of Na+/H+
RT exchanger.";
RL J. Biol. Chem. 277:43771-43777(2002).
RN [17]
RP INTERACTION WITH TESC AND CALMODULIN.
RX PubMed=12809501; DOI=10.1021/bi027143d;
RA Li X., Liu Y., Kay C.M., Muller-Esterl W., Fliegel L.;
RT "The Na+/H+ exchanger cytoplasmic tail: structure, function, and
RT interactions with tescalcin.";
RL Biochemistry 42:7448-7456(2003).
RN [18]
RP FUNCTION IN PH REGULATION, INTERACTION WITH CHP1, AND SUBCELLULAR LOCATION.
RX PubMed=15035633; DOI=10.1021/bi0360004;
RA Pang T., Hisamitsu T., Mori H., Shigekawa M., Wakabayashi S.;
RT "Role of calcineurin B homologous protein in pH regulation by the Na+/H+
RT exchanger 1: tightly bound Ca2+ ions as important structural elements.";
RL Biochemistry 43:3628-3636(2004).
RN [19]
RP MUTAGENESIS OF PRO-167 AND PRO-168.
RX PubMed=14680478; DOI=10.1042/bj20030884;
RA Slepkov E.R., Chow S., Lemieux M.J., Fliegel L.;
RT "Proline residues in transmembrane segment IV are critical for activity,
RT expression and targeting of the Na+/H+ exchanger isoform 1.";
RL Biochem. J. 379:31-38(2004).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-703, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-697; SER-703; SER-723;
RP SER-726; SER-729 AND SER-785, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-703, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-703, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
RP INTERACTION WITH CHP2, AND SUBCELLULAR LOCATION.
RX PubMed=21392185; DOI=10.1111/j.1365-2443.2011.01497.x;
RA Li Q.H., Wang L.H., Lin Y.N., Chang G.Q., Li H.W., Jin W.N., Hu R.H.,
RA Pang T.X.;
RT "Nuclear accumulation of calcineurin B homologous protein 2 (CHP2) results
RT in enhanced proliferation of tumor cells.";
RL Genes Cells 16:416-426(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-703, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-602; SER-605; SER-693;
RP SER-703 AND SER-785, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-599; SER-602 AND SER-703, AND
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).
RN [29]
RP INTERACTION WITH TESC AND CALM1, AND MUTAGENESIS OF 526-PHE--LEU-531.
RX PubMed=30287853; DOI=10.1038/s41598-018-33096-5;
RA Fuchs S., Hansen S.C., Markones M., Mymrikov E.V., Heerklotz H., Hunte C.;
RT "Calcineurin B homologous protein 3 binds with high affinity to the CHP
RT binding domain of the human sodium/proton exchanger NHE1.";
RL Sci. Rep. 8:14837-14837(2018).
RN [30]
RP INVOLVEMENT IN LIKNS, VARIANT LIKNS ARG-305, AND CHARACTERIZATION OF
RP VARIANT LIKNS ARG-305.
RX PubMed=25205112; DOI=10.1093/hmg/ddu461;
RA Guissart C., Li X., Leheup B., Drouot N., Montaut-Verient B., Raffo E.,
RA Jonveaux P., Roux A.F., Claustres M., Fliegel L., Koenig M.;
RT "Mutation of SLC9A1, encoding the major Na[?]/H[?] exchanger, causes
RT ataxia-deafness Lichtenstein-Knorr syndrome.";
RL Hum. Mol. Genet. 24:463-470(2015).
RN [31]
RP STRUCTURE BY NMR OF 155-180, AND MUTAGENESIS OF PHE-155; LEU-156; GLN-157;
RP SER-158; ASP-159; VAL-160; PHE-161; PHE-162; LEU-163; PHE-164; LEU-165;
RP LEU-166; PRO-167; PRO-168; ILE-169; ILE-170; LEU-171; ASP-172; ALA-173;
RP GLY-174; TYR-175; PHE-176 AND LEU-177.
RX PubMed=15677483; DOI=10.1074/jbc.m409608200;
RA Slepkov E.R., Rainey J.K., Li X., Liu Y., Cheng F.J., Lindhout D.A.,
RA Sykes B.D., Fliegel L.;
RT "Structural and functional characterization of transmembrane segment IV of
RT the NHE1 isoform of the Na+/H+ exchanger.";
RL J. Biol. Chem. 280:17863-17872(2005).
RN [32]
RP PRELIMINARY X-RAY CRYSTALLOGRAPHY OF 503-545 IN COMPLEX WITH CHP2.
RX PubMed=16511206; DOI=10.1107/s1744309105030836;
RA Ben Ammar Y., Takeda S., Sugawara M., Miyano M., Mori H., Wakabayashi S.;
RT "Crystallization and preliminary crystallographic analysis of the human
RT calcineurin homologous protein CHP2 bound to the cytoplasmic region of the
RT Na+/H+ exchanger NHE1.";
RL Acta Crystallogr. F 61:956-958(2005).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 503-545 IN COMPLEX WITH CHP2, AND
RP MUTAGENESIS OF ILE-534 AND ILE-537.
RX PubMed=16710297; DOI=10.1038/sj.emboj.7601145;
RA Ammar Y.B., Takeda S., Hisamitsu T., Mori H., Wakabayashi S.;
RT "Crystal structure of CHP2 complexed with NHE1-cytosolic region and an
RT implication for pH regulation.";
RL EMBO J. 25:2315-2325(2006).
RN [34]
RP STRUCTURE BY NMR OF 503-545 IN COMPLEX WITH CHP1.
RX PubMed=17050540; DOI=10.1074/jbc.m604092200;
RA Mishima M., Wakabayashi S., Kojima C.;
RT "Solution structure of the cytoplasmic region of Na+/H+ exchanger 1
RT complexed with essential cofactor calcineurin B homologous protein 1.";
RL J. Biol. Chem. 282:2741-2751(2007).
RN [35]
RP VARIANT LIKNS GLU-313.
RX PubMed=30237576; DOI=10.1038/s41436-018-0138-x;
RA Maddirevula S., Alzahrani F., Al-Owain M., Al Muhaizea M.A., Kayyali H.R.,
RA AlHashem A., Rahbeeni Z., Al-Otaibi M., Alzaidan H.I., Balobaid A.,
RA El Khashab H.Y., Bubshait D.K., Faden M., Yamani S.A., Dabbagh O.,
RA Al-Mureikhi M., Jasser A.A., Alsaif H.S., Alluhaydan I., Seidahmed M.Z.,
RA Alabbasi B.H., Almogarri I., Kurdi W., Akleh H., Qari A., Al Tala S.M.,
RA Alhomaidi S., Kentab A.Y., Salih M.A., Chedrawi A., Alameer S., Tabarki B.,
RA Shamseldin H.E., Patel N., Ibrahim N., Abdulwahab F., Samira M., Goljan E.,
RA Abouelhoda M., Meyer B.F., Hashem M., Shaheen R., AlShahwan S.,
RA Alfadhel M., Ben-Omran T., Al-Qattan M.M., Monies D., Alkuraya F.S.;
RT "Autozygome and high throughput confirmation of disease genes candidacy.";
RL Genet. Med. 21:736-742(2019).
CC -!- FUNCTION: Involved in pH regulation to eliminate acids generated by
CC active metabolism or to counter adverse environmental conditions. Major
CC proton extruding system driven by the inward sodium ion chemical
CC gradient. Plays an important role in signal transduction.
CC {ECO:0000269|PubMed:11350981, ECO:0000269|PubMed:15035633,
CC ECO:0000269|PubMed:8901634}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Fully active at acidic pHs, the antiporter is virtually turned off at
CC neutral pH.;
CC -!- SUBUNIT: Oligomer (By similarity). Interacts with CALM1 in a calcium-
CC dependent manner (PubMed:12809501, PubMed:30287853). Interacts with
CC TESC (PubMed:11696366, PubMed:30287853, PubMed:12809501). Interacts
CC (via the juxtamembrane region of the cytoplasmic C-terminal domain)
CC with CHP1; the interaction occurs at the plasma membrane in a calcium-
CC dependent manner (PubMed:8967452, PubMed:8901634, PubMed:11350981,
CC PubMed:15035633, PubMed:17050540). Interacts with CHP2; the interaction
CC occurs in a calcium-dependent manner (PubMed:12226101, PubMed:16710297,
CC PubMed:21392185). {ECO:0000250|UniProtKB:P26431,
CC ECO:0000269|PubMed:11350981, ECO:0000269|PubMed:11696366,
CC ECO:0000269|PubMed:12226101, ECO:0000269|PubMed:12809501,
CC ECO:0000269|PubMed:15035633, ECO:0000269|PubMed:16710297,
CC ECO:0000269|PubMed:17050540, ECO:0000269|PubMed:21392185,
CC ECO:0000269|PubMed:30287853, ECO:0000269|PubMed:8901634,
CC ECO:0000269|PubMed:8967452}.
CC -!- INTERACTION:
CC P19634; Q99653: CHP1; NbExp=3; IntAct=EBI-743635, EBI-722721;
CC P19634; O43745: CHP2; NbExp=4; IntAct=EBI-743635, EBI-8525536;
CC P19634; Q96BS2: TESC; NbExp=4; IntAct=EBI-743635, EBI-740653;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC Endoplasmic reticulum membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. Cell membrane; Multi-pass membrane protein.
CC Note=Colocalizes with CHP1 at the reticulum endoplasmic (By
CC similarity). Colocalizes with CHP1 and CHP2 at the plasma membrane.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P19634-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P19634-2; Sequence=VSP_022101, VSP_022102;
CC -!- TISSUE SPECIFICITY: Kidney and intestine.
CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:8068684}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC Ubiquitination is reduced by CHP1 (By similarity). {ECO:0000250}.
CC -!- DISEASE: Lichtenstein-Knorr syndrome (LIKNS) [MIM:616291]: An autosomal
CC recessive neurologic disorder characterized by progressive cerebellar
CC ataxia and severe progressive sensorineural hearing loss.
CC {ECO:0000269|PubMed:25205112, ECO:0000269|PubMed:30237576}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: Inhibited by amiloride and 5-amino-substituted
CC derivatives and activated in a cooperative fashion by intracellular
CC H(+). In quiescent cells upon growth factor stimulation, the apparent
CC affinity for internal H(+) is increased, resulting in a persistent rise
CC in cytoplasmic pH.
CC -!- SIMILARITY: Belongs to the monovalent cation:proton antiporter 1 (CPA1)
CC transporter (TC 2.A.36) family. {ECO:0000305}.
CC -!- CAUTION: The region between transmembrane regions M4 and M5 and between
CC M6 and M7 (also termed intracellular loops IL2 and IL4, respectively)
CC seem to be localized at least in part in the membrane. The hydrophobic
CC region H10 is proposed to be located within the membrane.
CC {ECO:0000305}.
CC -!- CAUTION: Although PubMed:12809501 report that TESC-binding results in a
CC decrease in activity, studies with rat SLC9A1 show that TESC-binding
CC results in the maturation and accumulation of SLC9A1 at the cell
CC surface. {ECO:0000305}.
CC -!- CAUTION: The interacting region with TESC is conflicting: Interaction
CC with TESC has been reported via the juxtamembrane region of the
CC cytoplasmic C-terminal domain, including residues 503-545
CC (PubMed:11696366, PubMed:30287853). In contrast, another publication
CC has reported interaction with TESC via residues 633-815, the region of
CC the cytoplasmic C-terminus more distal to the membrane
CC (PubMed:12809501). {ECO:0000269|PubMed:11696366,
CC ECO:0000269|PubMed:12809501, ECO:0000269|PubMed:30287853}.
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DR EMBL; M81768; AAB59460.1; ALT_SEQ; mRNA.
DR EMBL; S68616; AAC60606.1; -; mRNA.
DR EMBL; AF141350; AAF21350.1; -; mRNA.
DR EMBL; AF141351; AAF21351.1; -; mRNA.
DR EMBL; AF141352; AAF21352.1; -; mRNA.
DR EMBL; AF141353; AAF21353.1; -; mRNA.
DR EMBL; AF141354; AAF21354.1; -; mRNA.
DR EMBL; AF141355; AAF21355.1; -; mRNA.
DR EMBL; AF141356; AAF21356.1; -; mRNA.
DR EMBL; AF141357; AAF21357.1; -; mRNA.
DR EMBL; AF141358; AAF21358.1; -; mRNA.
DR EMBL; AF141359; AAF21359.1; -; mRNA.
DR EMBL; AF146430; AAF25592.1; -; mRNA.
DR EMBL; AF146431; AAF25593.1; -; mRNA.
DR EMBL; AF146432; AAF25594.1; -; mRNA.
DR EMBL; AF146433; AAF25595.1; -; mRNA.
DR EMBL; AF146434; AAF25596.1; -; mRNA.
DR EMBL; AF146435; AAF25597.1; -; mRNA.
DR EMBL; AF146436; AAF25598.1; -; mRNA.
DR EMBL; AF146437; AAF25599.1; -; mRNA.
DR EMBL; AF146438; AAF25600.1; -; mRNA.
DR EMBL; AF146439; AAF25601.1; -; mRNA.
DR EMBL; AL590640; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL137860; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07773.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07774.1; -; Genomic_DNA.
DR EMBL; BC012121; AAH12121.1; -; mRNA.
DR CCDS; CCDS295.1; -. [P19634-1]
DR PIR; I57487; I57487.
DR RefSeq; NP_003038.2; NM_003047.4. [P19634-1]
DR PDB; 1Y4E; NMR; -; A=155-180.
DR PDB; 2BEC; X-ray; 2.70 A; B=503-545.
DR PDB; 2E30; NMR; -; B=503-545.
DR PDB; 2HTG; NMR; -; A=250-274.
DR PDB; 2KBV; NMR; -; A=447-472.
DR PDB; 2L0E; NMR; -; A=226-250.
DR PDB; 2MDF; NMR; -; A=226-274.
DR PDB; 2YGG; X-ray; 2.23 A; A=622-689.
DR PDB; 6BJF; NMR; -; A=431-443.
DR PDB; 6NUC; X-ray; 1.90 A; C=679-723.
DR PDB; 6NUF; X-ray; 1.90 A; C=679-723.
DR PDB; 6NUU; X-ray; 2.30 A; C=679-723.
DR PDB; 6ZBI; NMR; -; B/C=622-657.
DR PDB; 7DSV; EM; 3.40 A; A/B=87-558.
DR PDB; 7DSW; EM; 3.30 A; A/B=87-506.
DR PDB; 7DSX; EM; 3.50 A; A/B=85-593.
DR PDBsum; 1Y4E; -.
DR PDBsum; 2BEC; -.
DR PDBsum; 2E30; -.
DR PDBsum; 2HTG; -.
DR PDBsum; 2KBV; -.
DR PDBsum; 2L0E; -.
DR PDBsum; 2MDF; -.
DR PDBsum; 2YGG; -.
DR PDBsum; 6BJF; -.
DR PDBsum; 6NUC; -.
DR PDBsum; 6NUF; -.
DR PDBsum; 6NUU; -.
DR PDBsum; 6ZBI; -.
DR PDBsum; 7DSV; -.
DR PDBsum; 7DSW; -.
DR PDBsum; 7DSX; -.
DR AlphaFoldDB; P19634; -.
DR BMRB; P19634; -.
DR SMR; P19634; -.
DR BioGRID; 112438; 125.
DR IntAct; P19634; 38.
DR MINT; P19634; -.
DR STRING; 9606.ENSP00000263980; -.
DR BindingDB; P19634; -.
DR ChEMBL; CHEMBL2781; -.
DR DrugBank; DB00594; Amiloride.
DR DrugBank; DB06468; Cariporide.
DR DrugBank; DB02624; Homoserine Lactone.
DR DrugBank; DB01043; Memantine.
DR DrugCentral; P19634; -.
DR TCDB; 2.A.36.1.13; the monovalent cation:proton antiporter-1 (cpa1) family.
DR GlyGen; P19634; 6 sites.
DR iPTMnet; P19634; -.
DR PhosphoSitePlus; P19634; -.
DR BioMuta; SLC9A1; -.
DR DMDM; 127809; -.
DR CPTAC; CPTAC-1005; -.
DR EPD; P19634; -.
DR jPOST; P19634; -.
DR MassIVE; P19634; -.
DR MaxQB; P19634; -.
DR PaxDb; P19634; -.
DR PeptideAtlas; P19634; -.
DR PRIDE; P19634; -.
DR ProteomicsDB; 53683; -. [P19634-1]
DR ProteomicsDB; 53684; -. [P19634-2]
DR Antibodypedia; 30723; 273 antibodies from 37 providers.
DR DNASU; 6548; -.
DR Ensembl; ENST00000263980.8; ENSP00000263980.3; ENSG00000090020.11. [P19634-1]
DR Ensembl; ENST00000374086.3; ENSP00000363199.3; ENSG00000090020.11. [P19634-2]
DR GeneID; 6548; -.
DR KEGG; hsa:6548; -.
DR MANE-Select; ENST00000263980.8; ENSP00000263980.3; NM_003047.5; NP_003038.2.
DR UCSC; uc001bnm.5; human. [P19634-1]
DR CTD; 6548; -.
DR DisGeNET; 6548; -.
DR GeneCards; SLC9A1; -.
DR HGNC; HGNC:11071; SLC9A1.
DR HPA; ENSG00000090020; Tissue enhanced (salivary gland, stomach).
DR MalaCards; SLC9A1; -.
DR MIM; 107310; gene.
DR MIM; 616291; phenotype.
DR neXtProt; NX_P19634; -.
DR OpenTargets; ENSG00000090020; -.
DR Orphanet; 448251; Progressive autosomal recessive ataxia-deafness syndrome.
DR PharmGKB; PA35928; -.
DR VEuPathDB; HostDB:ENSG00000090020; -.
DR eggNOG; KOG1966; Eukaryota.
DR GeneTree; ENSGT00940000156338; -.
DR HOGENOM; CLU_005912_4_1_1; -.
DR InParanoid; P19634; -.
DR OMA; TPPFWAS; -.
DR PhylomeDB; P19634; -.
DR TreeFam; TF317212; -.
DR PathwayCommons; P19634; -.
DR Reactome; R-HSA-2160916; Hyaluronan uptake and degradation.
DR Reactome; R-HSA-425986; Sodium/Proton exchangers.
DR SignaLink; P19634; -.
DR SIGNOR; P19634; -.
DR BioGRID-ORCS; 6548; 15 hits in 1087 CRISPR screens.
DR ChiTaRS; SLC9A1; human.
DR EvolutionaryTrace; P19634; -.
DR GeneWiki; Sodium%E2%80%93hydrogen_antiporter_1; -.
DR GenomeRNAi; 6548; -.
DR Pharos; P19634; Tchem.
DR PRO; PR:P19634; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P19634; protein.
DR Bgee; ENSG00000090020; Expressed in parotid gland and 188 other tissues.
DR ExpressionAtlas; P19634; baseline and differential.
DR Genevisible; P19634; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0090533; C:cation-transporting ATPase complex; IDA:BHF-UCL.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0014704; C:intercalated disc; IEA:Ensembl.
DR GO; GO:0030027; C:lamellipodium; TAS:BHF-UCL.
DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0030315; C:T-tubule; IEA:Ensembl.
DR GO; GO:0048306; F:calcium-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0060090; F:molecular adaptor activity; TAS:BHF-UCL.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; TAS:BHF-UCL.
DR GO; GO:0015386; F:potassium:proton antiporter activity; IBA:GO_Central.
DR GO; GO:0030346; F:protein phosphatase 2B binding; IDA:BHF-UCL.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; TAS:BHF-UCL.
DR GO; GO:0015385; F:sodium:proton antiporter activity; IDA:UniProtKB.
DR GO; GO:0086040; F:sodium:proton antiporter activity involved in regulation of cardiac muscle cell membrane potential; TAS:BHF-UCL.
DR GO; GO:0015299; F:solute:proton antiporter activity; TAS:UniProtKB.
DR GO; GO:0086003; P:cardiac muscle cell contraction; IEA:Ensembl.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0016477; P:cell migration; TAS:BHF-UCL.
DR GO; GO:0071468; P:cellular response to acidic pH; IDA:BHF-UCL.
DR GO; GO:0071236; P:cellular response to antibiotic; IEA:Ensembl.
DR GO; GO:0070417; P:cellular response to cold; IEA:Ensembl.
DR GO; GO:0071257; P:cellular response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0071872; P:cellular response to epinephrine stimulus; IMP:BHF-UCL.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; TAS:BHF-UCL.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IDA:BHF-UCL.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0030011; P:maintenance of cell polarity; TAS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0070997; P:neuron death; IEA:Ensembl.
DR GO; GO:0045760; P:positive regulation of action potential; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0070886; P:positive regulation of calcineurin-NFAT signaling cascade; IDA:BHF-UCL.
DR GO; GO:1903281; P:positive regulation of calcium:sodium antiporter activity; IMP:BHF-UCL.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IMP:BHF-UCL.
DR GO; GO:0030307; P:positive regulation of cell growth; IEA:Ensembl.
DR GO; GO:0035794; P:positive regulation of mitochondrial membrane permeability; IEA:Ensembl.
DR GO; GO:0098735; P:positive regulation of the force of heart contraction; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0051259; P:protein complex oligomerization; ISS:UniProtKB.
DR GO; GO:1902600; P:proton transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0086036; P:regulation of cardiac muscle cell membrane potential; TAS:BHF-UCL.
DR GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; IMP:BHF-UCL.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; TAS:BHF-UCL.
DR GO; GO:0051453; P:regulation of intracellular pH; IDA:UniProtKB.
DR GO; GO:0006885; P:regulation of pH; IDA:UniProtKB.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IEA:Ensembl.
DR GO; GO:0051492; P:regulation of stress fiber assembly; TAS:BHF-UCL.
DR GO; GO:0086092; P:regulation of the force of heart contraction by cardiac conduction; IMP:BHF-UCL.
DR GO; GO:0010447; P:response to acidic pH; IDA:UniProtKB.
DR GO; GO:0035994; P:response to muscle stretch; IMP:BHF-UCL.
DR GO; GO:0036376; P:sodium ion export across plasma membrane; ISS:UniProtKB.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; IDA:BHF-UCL.
DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl.
DR DisProt; DP01241; -.
DR InterPro; IPR006153; Cation/H_exchanger.
DR InterPro; IPR018422; Cation/H_exchanger_CPA1.
DR InterPro; IPR004709; NaH_exchanger.
DR InterPro; IPR001970; NHE-1-like.
DR InterPro; IPR032103; NHE_CaM-bd.
DR PANTHER; PTHR10110; PTHR10110; 1.
DR PANTHER; PTHR10110:SF59; PTHR10110:SF59; 1.
DR Pfam; PF00999; Na_H_Exchanger; 1.
DR Pfam; PF16644; NEXCaM_BD; 1.
DR PRINTS; PR01084; NAHEXCHNGR.
DR PRINTS; PR01085; NAHEXCHNGR1.
DR TIGRFAMs; TIGR00840; b_cpa1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Antiport; Calmodulin-binding;
KW Cell membrane; Deafness; Disease variant; Endoplasmic reticulum;
KW Glycoprotein; Ion transport; Membrane; Neurodegeneration; Phosphoprotein;
KW Reference proteome; Sodium; Sodium transport; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..815
FT /note="Sodium/hydrogen exchanger 1"
FT /id="PRO_0000052347"
FT TOPO_DOM 1..12
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 13..33
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 34..105
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 106..127
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 128..129
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 130..149
FT /note="Helical; Name=M3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 150..154
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..174
FT /note="Helical; Name=M4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 175..191
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 192..211
FT /note="Helical; Name=M5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 212..227
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 228..247
FT /note="Helical; Name=M6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..256
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 257..276
FT /note="Helical; Name=M7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..294
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 295..315
FT /note="Helical; Name=M8"
FT /evidence="ECO:0000255"
FT TOPO_DOM 316..338
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 339..358
FT /note="Helical; Name=M9"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..381
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 382..402
FT /note="Name=H10"
FT /evidence="ECO:0000250"
FT TOPO_DOM 403..410
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 411..430
FT /note="Helical; Name=M10"
FT /evidence="ECO:0000255"
FT TOPO_DOM 431..448
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 449..470
FT /note="Helical; Name=M11"
FT /evidence="ECO:0000255"
FT TOPO_DOM 471..479
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 480..499
FT /note="Helical; Name=M12"
FT /evidence="ECO:0000255"
FT TOPO_DOM 500..815
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 42..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 503..545
FT /note="Interaction with TESC"
FT /evidence="ECO:0000269|PubMed:30287853"
FT REGION 515..545
FT /note="Interaction with CHP2"
FT /evidence="ECO:0000269|PubMed:21392185"
FT REGION 633..815
FT /note="Interaction with CALM1"
FT /evidence="ECO:0000269|PubMed:30287853"
FT REGION 633..815
FT /note="Interaction with TESC"
FT /evidence="ECO:0000269|PubMed:12809501"
FT REGION 744..815
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 767..794
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 161
FT /note="Channel pore-lining"
FT /evidence="ECO:0000305"
FT SITE 370
FT /note="Not glycosylated"
FT MOD_RES 599
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 602
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 603
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q61165"
FT MOD_RES 605
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 693
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 697
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 703
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 723
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 726
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 729
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 785
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 787
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61165"
FT MOD_RES 796
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26431"
FT CARBOHYD 42
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 56
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 61
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 62
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 68
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000255"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8068684"
FT VAR_SEQ 496..554
FT /note="GMTIRPLVDLLAVKKKQETKRSINEEIHTQFLDHLLTGIEDICGHYGHHHWK
FT DKLNRFN -> VLGQGRAGPCLGDPHRLFPWKERKACDLKCDSSPSSTTNLLCDLGRAT
FT PPFWASVSSIVK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022101"
FT VAR_SEQ 555..815
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_022102"
FT VARIANT 305
FT /note="G -> R (in LIKNS; causes reduced expression of the
FT mutant protein; hypoglycosylated; does not localize
FT properly at the plasma membrane; small residual activity;
FT dbSNP:rs786204831)"
FT /evidence="ECO:0000269|PubMed:25205112"
FT /id="VAR_073439"
FT VARIANT 313
FT /note="G -> E (in LIKNS; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30237576"
FT /id="VAR_082153"
FT VARIANT 682
FT /note="N -> K (in dbSNP:rs35703140)"
FT /id="VAR_050231"
FT MUTAGEN 155
FT /note="F->C: Almost complete loss of activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 156
FT /note="L->C: Almost complete loss of activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 157
FT /note="Q->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 158
FT /note="S->C: Almost complete loss of activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 159
FT /note="D->C: Almost complete loss of activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 160
FT /note="V->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 161
FT /note="F->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 162
FT /note="F->C: Almost complete loss of activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 163
FT /note="L->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 164
FT /note="F->C: Almost complete loss of activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 165
FT /note="L->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 166
FT /note="L->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 167
FT /note="P->A: Reduces activity."
FT /evidence="ECO:0000269|PubMed:14680478,
FT ECO:0000269|PubMed:15677483"
FT MUTAGEN 167
FT /note="P->C,G: Almost complete loss of activity. Reduces
FT membrane localization."
FT /evidence="ECO:0000269|PubMed:14680478,
FT ECO:0000269|PubMed:15677483"
FT MUTAGEN 168
FT /note="P->A,C: Almost complete loss of activity."
FT /evidence="ECO:0000269|PubMed:14680478,
FT ECO:0000269|PubMed:15677483"
FT MUTAGEN 168
FT /note="P->G: Reduces activity."
FT /evidence="ECO:0000269|PubMed:14680478,
FT ECO:0000269|PubMed:15677483"
FT MUTAGEN 169
FT /note="I->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 170
FT /note="I->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 171
FT /note="L->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 172
FT /note="D->C: Almost complete loss of activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 173
FT /note="A->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 174
FT /note="G->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 175
FT /note="Y->C: Almost complete loss of activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 176
FT /note="F->C: Almost complete loss of activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 177
FT /note="L->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:15677483"
FT MUTAGEN 178
FT /note="P->A: No effect."
FT MUTAGEN 180
FT /note="R->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:10713111"
FT MUTAGEN 181
FT /note="Q->C: Reduces activity."
FT /evidence="ECO:0000269|PubMed:10713111"
FT MUTAGEN 518
FT /note="I->Q: Reduces interaction with CHP1 and the exchange
FT activity; when associated with Q-522."
FT /evidence="ECO:0000269|PubMed:11350981"
FT MUTAGEN 522
FT /note="I->Q: Reduces interaction with CHP1 and the exchange
FT activity; when associated with Q-518."
FT /evidence="ECO:0000269|PubMed:11350981"
FT MUTAGEN 526..531
FT /note="FLDHLL->QQDHQQ: Inhibits interaction with CHP1 and
FT the exchange activity. CHPI does not localize at the cell
FT membrane. Abolishes interaction with TESC."
FT /evidence="ECO:0000269|PubMed:11350981,
FT ECO:0000269|PubMed:30287853"
FT MUTAGEN 526..531
FT /note="FLDHLL->RRDHRR: Inhibits interaction with CHP1 and
FT the exchange activity. CHPI does not localize at the cell
FT membrane."
FT /evidence="ECO:0000269|PubMed:11350981"
FT MUTAGEN 526
FT /note="F->Q: Reduces interaction with CHP1 and the exchange
FT activity; when associated with Q-527."
FT /evidence="ECO:0000269|PubMed:11350981"
FT MUTAGEN 527
FT /note="L->Q: Reduces interaction with CHP1 and the exchange
FT activity; when associated with Q-526."
FT /evidence="ECO:0000269|PubMed:11350981"
FT MUTAGEN 530
FT /note="L->Q: Reduces interaction with CHP1 and the exchange
FT activity; when associated with Q-531."
FT /evidence="ECO:0000269|PubMed:11350981"
FT MUTAGEN 531
FT /note="L->Q: Reduces interaction with CHP1 and the exchange
FT activity; when associated with Q-530."
FT /evidence="ECO:0000269|PubMed:11350981"
FT MUTAGEN 534
FT /note="I->D,K: Strongly reduced interaction with CHP2."
FT /evidence="ECO:0000269|PubMed:16710297"
FT MUTAGEN 537
FT /note="I->K: Strongly reduced interaction with CHP2."
FT /evidence="ECO:0000269|PubMed:16710297"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:7DSW"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 101..120
FT /evidence="ECO:0007829|PDB:7DSW"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 131..149
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 160..164
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 166..175
FT /evidence="ECO:0007829|PDB:7DSW"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 186..214
FT /evidence="ECO:0007829|PDB:7DSW"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 225..234
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 239..245
FT /evidence="ECO:0007829|PDB:7DSW"
FT TURN 247..250
FT /evidence="ECO:0007829|PDB:7DSX"
FT HELIX 253..280
FT /evidence="ECO:0007829|PDB:7DSW"
FT STRAND 282..285
FT /evidence="ECO:0007829|PDB:7DSX"
FT HELIX 288..320
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:7DSX"
FT HELIX 330..347
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 352..366
FT /evidence="ECO:0007829|PDB:7DSW"
FT STRAND 367..371
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 373..403
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 411..436
FT /evidence="ECO:0007829|PDB:7DSW"
FT TURN 437..439
FT /evidence="ECO:0007829|PDB:7DSW"
FT STRAND 440..442
FT /evidence="ECO:0007829|PDB:7DSV"
FT HELIX 446..453
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 462..467
FT /evidence="ECO:0007829|PDB:7DSW"
FT STRAND 471..473
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 477..493
FT /evidence="ECO:0007829|PDB:7DSW"
FT TURN 494..498
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 500..504
FT /evidence="ECO:0007829|PDB:7DSW"
FT HELIX 518..538
FT /evidence="ECO:0007829|PDB:2BEC"
FT HELIX 544..557
FT /evidence="ECO:0007829|PDB:7DSV"
FT STRAND 558..562
FT /evidence="ECO:0007829|PDB:7DSX"
FT HELIX 572..590
FT /evidence="ECO:0007829|PDB:7DSX"
FT HELIX 625..651
FT /evidence="ECO:0007829|PDB:2YGG"
FT HELIX 658..681
FT /evidence="ECO:0007829|PDB:2YGG"
FT TURN 682..684
FT /evidence="ECO:0007829|PDB:2YGG"
FT STRAND 716..720
FT /evidence="ECO:0007829|PDB:6NUC"
SQ SEQUENCE 815 AA; 90763 MW; 02EC748C79DF6526 CRC64;
MVLRSGICGL SPHRIFPSLL VVVALVGLLP VLRSHGLQLS PTASTIRSSE PPRERSIGDV
TTAPPEVTPE SRPVNHSVTD HGMKPRKAFP VLGIDYTHVR TPFEISLWIL LACLMKIGFH
VIPTISSIVP ESCLLIVVGL LVGGLIKGVG ETPPFLQSDV FFLFLLPPII LDAGYFLPLR
QFTENLGTIL IFAVVGTLWN AFFLGGLMYA VCLVGGEQIN NIGLLDNLLF GSIISAVDPV
AVLAVFEEIH INELLHILVF GESLLNDAVT VVLYHLFEEF ANYEHVGIVD IFLGFLSFFV
VALGGVLVGV VYGVIAAFTS RFTSHIRVIE PLFVFLYSYM AYLSAELFHL SGIMALIASG
VVMRPYVEAN ISHKSHTTIK YFLKMWSSVS ETLIFIFLGV STVAGSHHWN WTFVISTLLF
CLIARVLGVL GLTWFINKFR IVKLTPKDQF IIAYGGLRGA IAFSLGYLLD KKHFPMCDLF
LTAIITVIFF TVFVQGMTIR PLVDLLAVKK KQETKRSINE EIHTQFLDHL LTGIEDICGH
YGHHHWKDKL NRFNKKYVKK CLIAGERSKE PQLIAFYHKM EMKQAIELVE SGGMGKIPSA
VSTVSMQNIH PKSLPSERIL PALSKDKEEE IRKILRNNLQ KTRQRLRSYN RHTLVADPYE
EAWNQMLLRR QKARQLEQKI NNYLTVPAHK LDSPTMSRAR IGSDPLAYEP KEDLPVITID
PASPQSPESV DLVNEELKGK VLGLSRDPAK VAEEDEDDDG GIMMRSKETS SPGTDDVFTP
APSDSPSSQR IQRCLSDPGP HPEPGEGEPF FPKGQ
