NHRF1_HUMAN
ID NHRF1_HUMAN Reviewed; 358 AA.
AC O14745; B3KY21; O43552; Q86WQ5;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Na(+)/H(+) exchange regulatory cofactor NHE-RF1 {ECO:0000305};
DE Short=NHERF-1;
DE AltName: Full=Ezrin-radixin-moesin-binding phosphoprotein 50;
DE Short=EBP50;
DE AltName: Full=Regulatory cofactor of Na(+)/H(+) exchanger;
DE AltName: Full=Sodium-hydrogen exchanger regulatory factor 1;
DE AltName: Full=Solute carrier family 9 isoform A3 regulatory factor 1;
GN Name=SLC9A3R1 {ECO:0000312|HGNC:HGNC:11075}; Synonyms=NHERF, NHERF1;
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] (ISOFORM 1), PROTEIN SEQUENCE OF 19-32 AND
RP 341-350, PHOSPHORYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH EZR AND MSN.
RX PubMed=9314537; DOI=10.1083/jcb.139.1.169;
RA Reczek D., Berryman M., Bretscher A.;
RT "Identification of EBP50: a PDZ-containing phosphoprotein that associates
RT with members of the ezrin-radixin-moesin family.";
RL J. Cell Biol. 139:169-179(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH EZR; RDX AND MSN.
RC TISSUE=Fetal brain;
RX PubMed=9430655; DOI=10.1074/jbc.273.3.1273;
RA Murthy A., Gonzalez-Agosti C., Cordero E., Pinney D., Candia C.,
RA Solomon F., Gusella J., Ramesh V.;
RT "NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common
RT interactor for merlin and ERM (MERM) proteins.";
RL J. Biol. Chem. 273:1273-1276(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Liver;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Blood, Lymph, Pancreas, and 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 [7]
RP PROTEIN SEQUENCE OF 2-13.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [8]
RP PROTEIN SEQUENCE OF 2-12; 39-49 AND 89-100, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=T-cell;
RA Bienvenut W.V., Kanor S., Tissot J.-D., Quadroni M.;
RL Submitted (MAY-2006) to UniProtKB.
RN [9]
RP FUNCTION, INTERACTION WITH SLC9A3, AND TISSUE SPECIFICITY.
RX PubMed=9096337; DOI=10.1073/pnas.94.7.3010;
RA Yun C.H.C., Oh S., Zizak M., Steplock D., Tsao S., Tse C.-M., Weinman E.J.,
RA Donowitz M.;
RT "cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger,
RT NHE3, requires an associated regulatory protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:3010-3015(1997).
RN [10]
RP FUNCTION, AND INTERACTION WITH ADRB2.
RX PubMed=10499588; DOI=10.1038/45816;
RA Cao T.T., Deacon H.W., Reczek D., Bretscher A., von Zastrow M.;
RT "A kinase-regulated PDZ-domain interaction controls endocytic sorting of
RT the beta2-adrenergic receptor.";
RL Nature 401:286-290(1999).
RN [11]
RP INTERACTION WITH PAG1, AND SUBCELLULAR LOCATION.
RX PubMed=11684085; DOI=10.1016/s0014-5793(01)02955-6;
RA Brdickova N., Brdicka T., Andera L., Spicka J., Angelisova P.,
RA Milgram S.L., Horejsi V.;
RT "Interaction between two adapter proteins, PAG and EBP50: a possible link
RT between membrane rafts and actin cytoskeleton.";
RL FEBS Lett. 507:133-136(2001).
RN [12]
RP INTERACTION WITH EPI64; ARHGAP17; PLCB3 AND EZR.
RX PubMed=11285285; DOI=10.1083/jcb.153.1.191;
RA Reczek D., Bretscher A.;
RT "Identification of EPI64, a TBC/rabGAP domain-containing microvillar
RT protein that binds to the first PDZ domain of EBP50 and E3KARP.";
RL J. Cell Biol. 153:191-206(2001).
RN [13]
RP INTERACTION WITH RACK1.
RX PubMed=11956211; DOI=10.1074/jbc.m201917200;
RA Liedtke C.M., Yun C.H.C., Kyle N., Wang D.;
RT "Protein kinase C epsilon-dependent regulation of cystic fibrosis
RT transmembrane regulator involves binding to a receptor for activated C
RT kinase (RACK1) and RACK1 binding to Na+/H+ exchange regulatory factor.";
RL J. Biol. Chem. 277:22925-22933(2002).
RN [14]
RP INTERACTION WITH OPRK1.
RX PubMed=12004055; DOI=10.1074/jbc.m200058200;
RA Li J.-G., Chen C., Liu-Chen L.-Y.;
RT "Ezrin-radixin-moesin-binding phosphoprotein-50/Na+/H+ exchanger regulatory
RT factor (EBP50/NHERF) blocks U50,488H-induced down-regulation of the human
RT kappa opioid receptor by enhancing its recycling rate.";
RL J. Biol. Chem. 277:27545-27552(2002).
RN [15]
RP INTERACTION WITH NOS2.
RX PubMed=12080081; DOI=10.1074/jbc.m205764200;
RA Glynne P.A., Darling K.E.A., Picot J., Evans T.J.;
RT "Epithelial inducible nitric-oxide synthase is an apical EBP50-binding
RT protein that directs vectorial nitric oxide output.";
RL J. Biol. Chem. 277:33132-33138(2002).
RN [16]
RP INTERACTION WITH GNAQ.
RX PubMed=12193606; DOI=10.1074/jbc.m207910200;
RA Rochdi M.D., Watier V., La Madeleine C., Nakata H., Kozasa T.,
RA Parent J.-L.;
RT "Regulation of GTP-binding protein alpha q (Galpha q) signaling by the
RT ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50).";
RL J. Biol. Chem. 277:40751-40759(2002).
RN [17]
RP INTERACTION WITH SLC4A7 AND CFTR.
RX PubMed=12403779; DOI=10.1074/jbc.m201862200;
RA Park M., Ko S.B.H., Choi J.Y., Muallem G., Thomas P.J., Pushkin A.,
RA Lee M.-S., Kim J.Y., Lee M.G., Muallem S., Kurtz I.;
RT "The cystic fibrosis transmembrane conductance regulator interacts with and
RT regulates the activity of the HCO3- salvage transporter human Na+-HCO3-
RT cotransport isoform 3.";
RL J. Biol. Chem. 277:50503-50509(2002).
RN [18]
RP INTERACTION WITH TRPC4.
RX PubMed=12154080; DOI=10.1242/jcs.115.17.3497;
RA Mery L., Strauss B., Dufour J.F., Krause K.H., Hoth M.;
RT "The PDZ-interacting domain of TRPC4 controls its localization and surface
RT expression in HEK293 cells.";
RL J. Cell Sci. 115:3497-3508(2002).
RN [19]
RP INDUCTION BY ESTROGEN.
RX PubMed=12145337; DOI=10.1210/me.2001-0290;
RA Ediger T.R., Park S.-E., Katzenellenbogen B.S.;
RT "Estrogen receptor inducibility of the human Na+/H+ exchanger regulatory
RT factor/ezrin-radixin-moesin binding protein 50 (NHE-RF/EBP50) gene
RT involving multiple half-estrogen response elements.";
RL Mol. Endocrinol. 16:1828-1839(2002).
RN [20]
RP INTERACTION WITH SLC4A7 AND ATP6V1B1.
RX PubMed=12444018; DOI=10.1152/ajpcell.00225.2002;
RA Pushkin A., Abuladze N., Newman D., Muronets V., Sassani P., Tatishchev S.,
RA Kurtz I.;
RT "The COOH termini of NBC3 and the 56-kDa H+-ATPase subunit are PDZ motifs
RT involved in their interaction.";
RL Am. J. Physiol. 284:C667-C673(2003).
RN [21]
RP INTERACTION WITH SLC26A6.
RX PubMed=12444019; DOI=10.1152/ajpcell.00270.2002;
RA Lohi H., Lamprecht G., Markovich D., Heil A., Kujala M., Seidler U.,
RA Kere J.;
RT "Isoforms of SLC26A6 mediate anion transport and have functional PDZ
RT interaction domains.";
RL Am. J. Physiol. 284:C769-C779(2003).
RN [22]
RP INTERACTION WITH CTNNB1.
RX PubMed=12830000; DOI=10.1053/jhep.2003.50270;
RA Shibata T., Chuma M., Kokubu A., Sakamoto M., Hirohashi S.;
RT "EBP50, a beta-catenin-associating protein, enhances Wnt signaling and is
RT over-expressed in hepatocellular carcinoma.";
RL Hepatology 38:178-186(2003).
RN [23]
RP INTERACTION WITH CLCN3.
RX PubMed=12471024; DOI=10.1074/jbc.m211050200;
RA Gentzsch M., Cui L., Mengos A., Chang X.-B., Chen J.-H., Riordan J.R.;
RT "The PDZ-binding chloride channel ClC-3B localizes to the Golgi and
RT associates with cystic fibrosis transmembrane conductance regulator-
RT interacting PDZ proteins.";
RL J. Biol. Chem. 278:6440-6449(2003).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells
RT and high confident phosphopeptide identification by cross-validation of
RT MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280, 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 [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [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 [30]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [31]
RP INTERACTION WITH MCC.
RX PubMed=19555689; DOI=10.1016/j.febslet.2009.06.034;
RA Arnaud C., Sebbagh M., Nola S., Audebert S., Bidaut G., Hermant A.,
RA Gayet O., Dusetti N.J., Ollendorff V., Santoni M.J., Borg J.P., Lecine P.;
RT "MCC, a new interacting protein for Scrib, is required for cell migration
RT in epithelial cells.";
RL FEBS Lett. 583:2326-2332(2009).
RN [32]
RP IDENTIFICATION BY 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 [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46 AND SER-280, AND
RP IDENTIFICATION BY 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 [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162; SER-269 AND SER-280, AND
RP IDENTIFICATION BY 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 [36]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [37]
RP INTERACTION WITH SLC34A1, VARIANT NPHLOP2 ALA-68, AND CHARACTERIZATION OF
RP VARIANT NPHLOP2 ALA-68.
RX PubMed=22506049; DOI=10.1371/journal.pone.0034764;
RA Courbebaisse M., Leroy C., Bakouh N., Salaun C., Beck L., Grandchamp B.,
RA Planelles G., Hall R.A., Friedlander G., Prie D.;
RT "A new human NHERF1 mutation decreases renal phosphate transporter NPT2a
RT expression by a PTH-independent mechanism.";
RL PLoS ONE 7:E34764-E34764(2012).
RN [38]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [39]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-46 AND SER-280, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [40]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-269; SER-280 AND SER-294, 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 [41]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [42]
RP INTERACTION WITH ACE2, AND MUTAGENESIS OF 24-TYR--PHE-26 AND
RP 164-TYR--PHE-166.
RX PubMed=34189428; DOI=10.1016/j.isci.2021.102770;
RA Zhang Q., Gefter J., Sneddon W.B., Mamonova T., Friedman P.A.;
RT "ACE2 interaction with cytoplasmic PDZ protein enhances SARS-CoV-2
RT invasion.";
RL IScience 24:102770-102770(2021).
RN [43]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 11-99 IN COMPLEX WITH CFTR.
RX PubMed=11304524; DOI=10.1074/jbc.c100154200;
RA Karthikeyan S., Leung T., Ladias J.A.A.;
RT "Structural basis of the Na+/H+ exchanger regulatory factor PDZ1
RT interaction with the carboxyl-terminal region of the cystic fibrosis
RT transmembrane conductance regulator.";
RL J. Biol. Chem. 276:19683-19686(2001).
RN [44]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 11-99, AND HOMODIMERIZATION.
RX PubMed=11352585; DOI=10.1006/jmbi.2001.4634;
RA Karthikeyan S., Leung T., Birrane G., Webster G., Ladias J.A.A.;
RT "Crystal structure of the PDZ1 domain of human Na(+)/H(+) exchanger
RT regulatory factor provides insights into the mechanism of carboxyl-terminal
RT leucine recognition by class I PDZ domains.";
RL J. Mol. Biol. 308:963-973(2001).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 11-99 IN COMPLEX WITH PDGFRA;
RP PDGFRB OR ADRB2.
RX PubMed=11882663; DOI=10.1074/jbc.m201507200;
RA Karthikeyan S., Leung T., Ladias J.A.A.;
RT "Structural determinants of the Na+/H+ exchanger regulatory factor
RT interaction with the beta 2 adrenergic and platelet-derived growth factor
RT receptors.";
RL J. Biol. Chem. 277:18973-18978(2002).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 321-358 IN COMPLEX WITH MSX, AND
RP MUTAGENESIS OF PHE-355 AND LEU-358.
RX PubMed=15020681; DOI=10.1242/jcs.01038;
RA Finnerty C.M., Chambers D., Ingraffea J., Faber H.R., Karplus P.A.,
RA Bretscher A.;
RT "The EBP50-moesin interaction involves a binding site regulated by direct
RT masking on the FERM domain.";
RL J. Cell Sci. 117:1547-1552(2004).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 331-358 IN COMPLEX WITH RDX.
RX PubMed=16615918; DOI=10.1016/j.str.2006.01.015;
RA Terawaki S., Maesaki R., Hakoshima T.;
RT "Structural basis for NHERF recognition by ERM proteins.";
RL Structure 14:777-789(2006).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 150-236.
RG Structural genomics consortium (SGC);
RT "The crystal structure of the 2nd PDZ domain of the human NHERF-1
RT (SLC9A3R1).";
RL Submitted (MAR-2007) to the PDB data bank.
RN [49]
RP FUNCTION IN RENAL PHOSPHATE ABSORPTION, VARIANTS NPHLOP2 VAL-110; GLN-153
RP AND LYS-225, AND CHARACTERIZATION OF VARIANTS NPHLOP2 VAL-110; GLN-153 AND
RP LYS-225.
RX PubMed=18784102; DOI=10.1056/nejmoa0802836;
RA Karim Z., Gerard B., Bakouh N., Alili R., Leroy C., Beck L., Silve C.,
RA Planelles G., Urena-Torres P., Grandchamp B., Friedlander G., Prie D.;
RT "NHERF1 mutations and responsiveness of renal parathyroid hormone.";
RL N. Engl. J. Med. 359:1128-1135(2008).
CC -!- FUNCTION: Scaffold protein that connects plasma membrane proteins with
CC members of the ezrin/moesin/radixin family and thereby helps to link
CC them to the actin cytoskeleton and to regulate their surface
CC expression. Necessary for recycling of internalized ADRB2. Was first
CC known to play a role in the regulation of the activity and subcellular
CC location of SLC9A3. Necessary for cAMP-mediated phosphorylation and
CC inhibition of SLC9A3. May enhance Wnt signaling. May participate in
CC HTR4 targeting to microvilli (By similarity). Involved in the
CC regulation of phosphate reabsorption in the renal proximal tubules.
CC Involved in sperm capacitation. May participate in the regulation of
CC the chloride and bicarbonate homeostasis in spermatozoa. {ECO:0000250,
CC ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:18784102,
CC ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9430655}.
CC -!- SUBUNIT: Homodimer, and heterodimer with SLC9A3R2. Binds the N-termini
CC of EZR, RDX and MSN. Binds the C-termini of PDGFRA, PDGFRB, ADRB2, NOS2
CC and CFTR. Binds ARHGAP17, EPI64, RACK1, OPRK1, GNAQ, CTNNB1 and PLCB3.
CC Binds PDZK1 (By similarity). Interacts with CLCN3. Binds the C-terminus
CC of PAG1. In resting T-cells, part of a PAG1-SLC9A3R1-MSN complex which
CC is disrupted upon TCR activation. Forms a complex with CFTR and SLC4A7.
CC Forms a complex with SLC4A7 and ATP6V1B1. Interacts with TRPC4 (via the
CC PDZ-binding domain). Directly interacts with HTR4 (By similarity).
CC Interacts (via the PDZ 1 domain) with PODXL (via the C-terminal PDZ-
CC binding motif DTHL); interaction is not detected in glomerular
CC epithelium cells. Interacts (via the PDZ 1 domain) with PODXL (via the
CC C-terminal PDZ-binding motif DTHL); the interaction take place early in
CC the secretory pathway and is necessary for its apical membrane sorting
CC (By similarity). Interacts with SLC26A3 (By similarity). Interacts with
CC MCC. Interacts with SLC34A1. Interacts (via the PDZ domains) with
CC SLC26A6 isoform 4 and isoform 5. Interacts (via PDZ domains) with ACE2
CC (via PDZ-binding motif); the interaction may enhance ACE2 membrane
CC residence (PubMed:34189428). {ECO:0000250|UniProtKB:P70441,
CC ECO:0000269|PubMed:10499588, ECO:0000269|PubMed:11285285,
CC ECO:0000269|PubMed:11304524, ECO:0000269|PubMed:11684085,
CC ECO:0000269|PubMed:11882663, ECO:0000269|PubMed:11956211,
CC ECO:0000269|PubMed:12004055, ECO:0000269|PubMed:12080081,
CC ECO:0000269|PubMed:12154080, ECO:0000269|PubMed:12193606,
CC ECO:0000269|PubMed:12403779, ECO:0000269|PubMed:12444018,
CC ECO:0000269|PubMed:12444019, ECO:0000269|PubMed:12471024,
CC ECO:0000269|PubMed:12830000, ECO:0000269|PubMed:15020681,
CC ECO:0000269|PubMed:16615918, ECO:0000269|PubMed:19555689,
CC ECO:0000269|PubMed:22506049, ECO:0000269|PubMed:34189428,
CC ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9314537,
CC ECO:0000269|PubMed:9430655}.
CC -!- INTERACTION:
CC O14745; Q9BYF1: ACE2; NbExp=7; IntAct=EBI-349787, EBI-7730807;
CC O14745; P07550: ADRB2; NbExp=6; IntAct=EBI-349787, EBI-491169;
CC O14745; Q92624: APPBP2; NbExp=3; IntAct=EBI-349787, EBI-743771;
CC O14745; P13569: CFTR; NbExp=15; IntAct=EBI-349787, EBI-349854;
CC O14745; P29762: CRABP1; NbExp=3; IntAct=EBI-349787, EBI-725950;
CC O14745; Q9Y2H0-1: DLGAP4; NbExp=3; IntAct=EBI-349787, EBI-12000556;
CC O14745; P15311: EZR; NbExp=6; IntAct=EBI-349787, EBI-1056902;
CC O14745; P26038: MSN; NbExp=4; IntAct=EBI-349787, EBI-528768;
CC O14745; P35240-1: NF2; NbExp=4; IntAct=EBI-349787, EBI-1014500;
CC O14745; P47900: P2RY1; NbExp=2; IntAct=EBI-349787, EBI-8677223;
CC O14745; P09619: PDGFRB; NbExp=5; IntAct=EBI-349787, EBI-641237;
CC O14745; O60346: PHLPP1; NbExp=2; IntAct=EBI-349787, EBI-2511516;
CC O14745; O60346-2: PHLPP1; NbExp=5; IntAct=EBI-349787, EBI-11165225;
CC O14745; Q6ZVD8: PHLPP2; NbExp=6; IntAct=EBI-349787, EBI-2511496;
CC O14745; P60484: PTEN; NbExp=7; IntAct=EBI-349787, EBI-696162;
CC O14745; O14745: SLC9A3R1; NbExp=2; IntAct=EBI-349787, EBI-349787;
CC O14745; Q9R0W0: mGluR1a; Xeno; NbExp=2; IntAct=EBI-349787, EBI-8505383;
CC O14745; P26043: Rdx; Xeno; NbExp=2; IntAct=EBI-349787, EBI-647737;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Apical cell membrane
CC {ECO:0000250}. Endomembrane system; Peripheral membrane protein. Cell
CC projection, filopodium. Cell projection, ruffle. Cell projection,
CC microvillus. Note=Translocates from the cytoplasm to the apical cell
CC membrane in a PODXL-dependent manner. Colocalizes with CFTR at the
CC midpiece of sperm tail (By similarity). Colocalizes with actin in
CC microvilli-rich apical regions of the syncytiotrophoblast. Found in
CC microvilli, ruffling membrane and filopodia of HeLa cells. Present in
CC lipid rafts of T-cells. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O14745-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O14745-2; Sequence=VSP_055497;
CC -!- TISSUE SPECIFICITY: Detected in liver, kidney, pancreas, prostate,
CC spleen, small intestine and placenta, in particular in the
CC syncytiotrophoblast. {ECO:0000269|PubMed:9096337,
CC ECO:0000269|PubMed:9314537}.
CC -!- INDUCTION: By estrogen. {ECO:0000269|PubMed:12145337}.
CC -!- PTM: Phosphorylated on serine residues. {ECO:0000269|PubMed:9314537}.
CC -!- DISEASE: Nephrolithiasis/osteoporosis, hypophosphatemic, 2 (NPHLOP2)
CC [MIM:612287]: A disease characterized by decreased renal phosphate
CC absorption, renal phosphate wasting, hypophosphatemia,
CC hyperphosphaturia, hypercalciuria, nephrolithiasis and osteoporosis.
CC {ECO:0000269|PubMed:18784102, ECO:0000269|PubMed:22506049}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH49220.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SLC9A3R1ID46023ch17q25.html";
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DR EMBL; AF015926; AAC52084.1; -; mRNA.
DR EMBL; AF036241; AAC04572.1; -; mRNA.
DR EMBL; AK128474; BAG54683.1; -; mRNA.
DR EMBL; AC016888; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89189.1; -; Genomic_DNA.
DR EMBL; BC001443; AAH01443.1; -; mRNA.
DR EMBL; BC003361; AAH03361.1; -; mRNA.
DR EMBL; BC011777; AAH11777.1; -; mRNA.
DR EMBL; BC049220; AAH49220.1; ALT_INIT; mRNA.
DR EMBL; BC053350; AAH53350.1; -; mRNA.
DR CCDS; CCDS11705.1; -. [O14745-1]
DR RefSeq; NP_004243.1; NM_004252.4. [O14745-1]
DR PDB; 1G9O; X-ray; 1.50 A; A=11-99.
DR PDB; 1GQ4; X-ray; 1.90 A; A=11-94.
DR PDB; 1GQ5; X-ray; 2.20 A; A=11-94.
DR PDB; 1I92; X-ray; 1.70 A; A=11-94.
DR PDB; 1SGH; X-ray; 3.50 A; B=321-358.
DR PDB; 2D10; X-ray; 2.50 A; E/F/G/H=331-358.
DR PDB; 2JXO; NMR; -; A=150-240.
DR PDB; 2KJD; NMR; -; A=150-270.
DR PDB; 2KRG; NMR; -; A=150-358.
DR PDB; 2M0T; NMR; -; A=11-120.
DR PDB; 2M0U; NMR; -; A=11-120.
DR PDB; 2M0V; NMR; -; A=150-270.
DR PDB; 2OZF; X-ray; 1.50 A; A=150-235.
DR PDB; 4JL7; X-ray; 1.16 A; A=11-95.
DR PDB; 4LMM; X-ray; 1.10 A; A=11-94.
DR PDB; 4MPA; X-ray; 1.10 A; A=11-94.
DR PDB; 4N6X; X-ray; 1.05 A; A=11-94.
DR PDB; 4PQW; X-ray; 1.47 A; A=11-94.
DR PDB; 4Q3H; X-ray; 1.44 A; A/B=150-234.
DR PDB; 6RQR; X-ray; 2.20 A; A/B=150-269.
DR PDBsum; 1G9O; -.
DR PDBsum; 1GQ4; -.
DR PDBsum; 1GQ5; -.
DR PDBsum; 1I92; -.
DR PDBsum; 1SGH; -.
DR PDBsum; 2D10; -.
DR PDBsum; 2JXO; -.
DR PDBsum; 2KJD; -.
DR PDBsum; 2KRG; -.
DR PDBsum; 2M0T; -.
DR PDBsum; 2M0U; -.
DR PDBsum; 2M0V; -.
DR PDBsum; 2OZF; -.
DR PDBsum; 4JL7; -.
DR PDBsum; 4LMM; -.
DR PDBsum; 4MPA; -.
DR PDBsum; 4N6X; -.
DR PDBsum; 4PQW; -.
DR PDBsum; 4Q3H; -.
DR PDBsum; 6RQR; -.
DR AlphaFoldDB; O14745; -.
DR SMR; O14745; -.
DR BioGRID; 114769; 153.
DR CORUM; O14745; -.
DR DIP; DIP-29092N; -.
DR ELM; O14745; -.
DR IntAct; O14745; 44.
DR MINT; O14745; -.
DR STRING; 9606.ENSP00000262613; -.
DR BindingDB; O14745; -.
DR ChEMBL; CHEMBL4523125; -.
DR TCDB; 8.A.24.1.1; the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family.
DR GlyGen; O14745; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O14745; -.
DR PhosphoSitePlus; O14745; -.
DR BioMuta; SLC9A3R1; -.
DR CPTAC; CPTAC-588; -.
DR CPTAC; CPTAC-589; -.
DR EPD; O14745; -.
DR jPOST; O14745; -.
DR MassIVE; O14745; -.
DR MaxQB; O14745; -.
DR PaxDb; O14745; -.
DR PeptideAtlas; O14745; -.
DR PRIDE; O14745; -.
DR ProteomicsDB; 48202; -. [O14745-1]
DR Antibodypedia; 1525; 347 antibodies from 37 providers.
DR DNASU; 9368; -.
DR Ensembl; ENST00000262613.10; ENSP00000262613.5; ENSG00000109062.12. [O14745-1]
DR Ensembl; ENST00000413388.2; ENSP00000464982.1; ENSG00000109062.12. [O14745-2]
DR GeneID; 9368; -.
DR KEGG; hsa:9368; -.
DR MANE-Select; ENST00000262613.10; ENSP00000262613.5; NM_004252.5; NP_004243.1.
DR UCSC; uc002jlo.5; human. [O14745-1]
DR CTD; 9368; -.
DR DisGeNET; 9368; -.
DR GeneCards; SLC9A3R1; -.
DR HGNC; HGNC:11075; SLC9A3R1.
DR HPA; ENSG00000109062; Tissue enhanced (esophagus).
DR MalaCards; SLC9A3R1; -.
DR MIM; 604990; gene.
DR MIM; 612287; phenotype.
DR neXtProt; NX_O14745; -.
DR OpenTargets; ENSG00000109062; -.
DR Orphanet; 244305; Dominant hypophosphatemia with nephrolithiasis or osteoporosis.
DR PharmGKB; PA35931; -.
DR VEuPathDB; HostDB:ENSG00000109062; -.
DR eggNOG; KOG3528; Eukaryota.
DR GeneTree; ENSGT00950000182849; -.
DR HOGENOM; CLU_038627_1_0_1; -.
DR InParanoid; O14745; -.
DR OMA; NGQIHGH; -.
DR OrthoDB; 880632at2759; -.
DR PhylomeDB; O14745; -.
DR TreeFam; TF350449; -.
DR PathwayCommons; O14745; -.
DR SignaLink; O14745; -.
DR SIGNOR; O14745; -.
DR BioGRID-ORCS; 9368; 12 hits in 1085 CRISPR screens.
DR ChiTaRS; SLC9A3R1; human.
DR EvolutionaryTrace; O14745; -.
DR GeneWiki; Sodium-hydrogen_antiporter_3_regulator_1; -.
DR GenomeRNAi; 9368; -.
DR Pharos; O14745; Tbio.
DR PRO; PR:O14745; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O14745; protein.
DR Bgee; ENSG00000109062; Expressed in granulocyte and 193 other tissues.
DR ExpressionAtlas; O14745; baseline and differential.
DR Genevisible; O14745; HS.
DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0071944; C:cell periphery; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005902; C:microvillus; IDA:UniProtKB.
DR GO; GO:0031528; C:microvillus membrane; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0098797; C:plasma membrane protein complex; ISS:ARUK-UCL.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0097225; C:sperm midpiece; ISS:UniProtKB.
DR GO; GO:0032426; C:stereocilium tip; IEA:Ensembl.
DR GO; GO:0031982; C:vesicle; HDA:UniProtKB.
DR GO; GO:0031698; F:beta-2 adrenergic receptor binding; IPI:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; IPI:UniProtKB.
DR GO; GO:0017081; F:chloride channel regulator activity; IDA:UniProtKB.
DR GO; GO:0050780; F:dopamine receptor binding; IEA:Ensembl.
DR GO; GO:0015185; F:gamma-aminobutyric acid transmembrane transporter activity; IEA:Ensembl.
DR GO; GO:0070851; F:growth factor receptor binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0045159; F:myosin II binding; IEA:Ensembl.
DR GO; GO:0030165; F:PDZ domain binding; IPI:UniProtKB.
DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
DR GO; GO:0043621; F:protein self-association; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB.
DR GO; GO:0031799; F:type 2 metabotropic glutamate receptor binding; IPI:ARUK-UCL.
DR GO; GO:0031800; F:type 3 metabotropic glutamate receptor binding; IPI:ARUK-UCL.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0007191; P:adenylate cyclase-activating dopamine receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; IEA:Ensembl.
DR GO; GO:0032782; P:bile acid secretion; ISS:UniProtKB.
DR GO; GO:0030643; P:cellular phosphate ion homeostasis; IEA:Ensembl.
DR GO; GO:0090660; P:cerebrospinal fluid circulation; ISS:ARUK-UCL.
DR GO; GO:0044782; P:cilium organization; ISS:ARUK-UCL.
DR GO; GO:0045198; P:establishment of epithelial cell apical/basal polarity; IMP:UniProtKB.
DR GO; GO:0051683; P:establishment of Golgi localization; IMP:UniProtKB.
DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl.
DR GO; GO:0051939; P:gamma-aminobutyric acid import; ISS:ARUK-UCL.
DR GO; GO:0022612; P:gland morphogenesis; IMP:UniProtKB.
DR GO; GO:0034635; P:glutathione transport; ISS:UniProtKB.
DR GO; GO:0098739; P:import across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0045199; P:maintenance of epithelial cell apical/basal polarity; IMP:ARUK-UCL.
DR GO; GO:0030033; P:microvillus assembly; IMP:UniProtKB.
DR GO; GO:0002009; P:morphogenesis of an epithelium; NAS:ARUK-UCL.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0010764; P:negative regulation of fibroblast migration; IEA:Ensembl.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:0032416; P:negative regulation of sodium:proton antiporter activity; IEA:Ensembl.
DR GO; GO:0007097; P:nuclear migration; IMP:UniProtKB.
DR GO; GO:0060158; P:phospholipase C-activating dopamine receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0007009; P:plasma membrane organization; ISS:ARUK-UCL.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:0034767; P:positive regulation of ion transmembrane transport; IEA:Ensembl.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0008361; P:regulation of cell size; IMP:UniProtKB.
DR GO; GO:0045859; P:regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:1903402; P:regulation of renal phosphate excretion; IEA:Ensembl.
DR GO; GO:0032415; P:regulation of sodium:proton antiporter activity; NAS:UniProtKB.
DR GO; GO:0070293; P:renal absorption; ISS:UniProtKB.
DR GO; GO:0097291; P:renal phosphate ion absorption; IMP:UniProtKB.
DR GO; GO:0003096; P:renal sodium ion transport; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR DisProt; DP02000; -.
DR Gene3D; 2.30.42.10; -; 2.
DR IDEAL; IID00134; -.
DR InterPro; IPR015098; EBP50_C-term.
DR InterPro; IPR031199; NHERF-1.
DR InterPro; IPR017300; NHERF-1/NHERF-2.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR PANTHER; PTHR14191:SF7; PTHR14191:SF7; 1.
DR Pfam; PF09007; EBP50_C; 1.
DR Pfam; PF00595; PDZ; 2.
DR PIRSF; PIRSF037866; EBP50; 1.
DR SMART; SM00228; PDZ; 2.
DR SUPFAM; SSF50156; SSF50156; 2.
DR PROSITE; PS50106; PDZ; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell membrane;
KW Cell projection; Cytoplasm; Direct protein sequencing; Disease variant;
KW Membrane; Phosphoprotein; Reference proteome; Repeat;
KW Wnt signaling pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801, ECO:0000269|Ref.8,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378, ECO:0007744|PubMed:25944712"
FT CHAIN 2..358
FT /note="Na(+)/H(+) exchange regulatory cofactor NHE-RF1"
FT /id="PRO_0000096799"
FT DOMAIN 14..94
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 154..234
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 114..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 277..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 134..155
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 286..322
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..348
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378,
FT ECO:0007744|PubMed:25944712"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 280
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:17924679, ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 290
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28619"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70441"
FT MOD_RES 293
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P70441"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70441"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70441"
FT VAR_SEQ 1..156
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055497"
FT VARIANT 68
FT /note="E -> A (in NPHLOP2; impairs the interaction with
FT SLC34A1; causes a reduction of SLC34A1 amount on cell
FT membrane and affects SLC34A1-dependent phosphate uptake;
FT dbSNP:rs139622189)"
FT /evidence="ECO:0000269|PubMed:22506049"
FT /id="VAR_067661"
FT VARIANT 110
FT /note="L -> V (in NPHLOP2; the mutant expressed in cultured
FT renal cells increases the generation of cyclic AMP (cAMP)
FT by parathyroid hormone (PTH) and inhibits phosphate
FT transport; dbSNP:rs35910969)"
FT /evidence="ECO:0000269|PubMed:18784102"
FT /id="VAR_034899"
FT VARIANT 153
FT /note="R -> Q (in NPHLOP2; the mutant expressed in cultured
FT renal cells increases the generation of cAMP by PTH and
FT inhibits phosphate transport; dbSNP:rs41282065)"
FT /evidence="ECO:0000269|PubMed:18784102"
FT /id="VAR_048021"
FT VARIANT 225
FT /note="E -> K (in NPHLOP2; the mutant expressed in cultured
FT renal cells increases the generation of cAMP by PTH and
FT inhibits phosphate transport; dbSNP:rs119486097)"
FT /evidence="ECO:0000269|PubMed:18784102"
FT /id="VAR_048022"
FT MUTAGEN 24..26
FT /note="YGF->AGA: Loss of interaction with ACE2."
FT /evidence="ECO:0000269|PubMed:34189428"
FT MUTAGEN 164..166
FT /note="YGF->AGA: Loss of interaction with ACE2."
FT /evidence="ECO:0000269|PubMed:34189428"
FT MUTAGEN 355
FT /note="F->R: Loss of MSX binding."
FT /evidence="ECO:0000269|PubMed:15020681"
FT MUTAGEN 358
FT /note="Missing: Reduces MSX binding."
FT /evidence="ECO:0000269|PubMed:15020681"
FT STRAND 13..18
FT /evidence="ECO:0007829|PDB:4N6X"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:4PQW"
FT STRAND 27..30
FT /evidence="ECO:0007829|PDB:4N6X"
FT STRAND 32..40
FT /evidence="ECO:0007829|PDB:4N6X"
FT HELIX 47..50
FT /evidence="ECO:0007829|PDB:4N6X"
FT STRAND 58..62
FT /evidence="ECO:0007829|PDB:4N6X"
FT HELIX 72..81
FT /evidence="ECO:0007829|PDB:4N6X"
FT STRAND 82..91
FT /evidence="ECO:0007829|PDB:4N6X"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:4N6X"
FT TURN 101..103
FT /evidence="ECO:0007829|PDB:2M0T"
FT TURN 106..108
FT /evidence="ECO:0007829|PDB:2M0T"
FT HELIX 109..112
FT /evidence="ECO:0007829|PDB:2M0T"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:2M0T"
FT STRAND 153..158
FT /evidence="ECO:0007829|PDB:4Q3H"
FT TURN 160..162
FT /evidence="ECO:0007829|PDB:2JXO"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:4Q3H"
FT STRAND 172..182
FT /evidence="ECO:0007829|PDB:4Q3H"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:2M0V"
FT HELIX 187..190
FT /evidence="ECO:0007829|PDB:4Q3H"
FT STRAND 198..202
FT /evidence="ECO:0007829|PDB:4Q3H"
FT HELIX 212..221
FT /evidence="ECO:0007829|PDB:4Q3H"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:4Q3H"
FT STRAND 225..231
FT /evidence="ECO:0007829|PDB:4Q3H"
FT HELIX 233..242
FT /evidence="ECO:0007829|PDB:6RQR"
FT HELIX 249..252
FT /evidence="ECO:0007829|PDB:6RQR"
FT HELIX 261..265
FT /evidence="ECO:0007829|PDB:6RQR"
FT STRAND 286..289
FT /evidence="ECO:0007829|PDB:2KRG"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:2KRG"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:2KRG"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:2KRG"
FT HELIX 323..328
FT /evidence="ECO:0007829|PDB:2KRG"
FT HELIX 329..333
FT /evidence="ECO:0007829|PDB:2KRG"
FT HELIX 348..355
FT /evidence="ECO:0007829|PDB:2D10"
SQ SEQUENCE 358 AA; 38868 MW; E33AF87016D37A65 CRC64;
MSADAAAGAP LPRLCCLEKG PNGYGFHLHG EKGKLGQYIR LVEPGSPAEK AGLLAGDRLV
EVNGENVEKE THQQVVSRIR AALNAVRLLV VDPETDEQLQ KLGVQVREEL LRAQEAPGQA
EPPAAAEVQG AGNENEPREA DKSHPEQREL RPRLCTMKKG PSGYGFNLHS DKSKPGQFIR
SVDPDSPAEA SGLRAQDRIV EVNGVCMEGK QHGDVVSAIR AGGDETKLLV VDRETDEFFK
KCRVIPSQEH LNGPLPVPFT NGEIQKENSR EALAEAALES PRPALVRSAS SDTSEELNSQ
DSPPKQDSTA PSSTSSSDPI LDFNISLAMA KERAHQKRSS KRAPQMDWSK KNELFSNL
