NHRF2_HUMAN
ID NHRF2_HUMAN Reviewed; 337 AA.
AC Q15599; D3DU84; D3DU85; H3BSV6; O00272; O00556; Q3KQY7;
DT 16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-FEB-2004, sequence version 2.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Na(+)/H(+) exchange regulatory cofactor NHE-RF2;
DE Short=NHERF-2;
DE AltName: Full=NHE3 kinase A regulatory protein E3KARP;
DE AltName: Full=SRY-interacting protein 1;
DE Short=SIP-1;
DE AltName: Full=Sodium-hydrogen exchanger regulatory factor 2;
DE AltName: Full=Solute carrier family 9 isoform A3 regulatory factor 2;
DE AltName: Full=Tyrosine kinase activator protein 1;
DE Short=TKA-1;
GN Name=SLC9A3R2; Synonyms=NHERF2;
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 2), INTERACTION WITH SRY, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Cervix carcinoma, Fetal brain, and Testis;
RX PubMed=9054412; DOI=10.1074/jbc.272.11.7167;
RA Poulat F., de Santa Barbara P., Desclozeaux M., Soullier S., Moniot B.,
RA Bonneaud N., Boizet B., Berta P.;
RT "The human testis determining factor SRY binds a nuclear factor containing
RT PDZ protein interaction domains.";
RL J. Biol. Chem. 272:7167-7172(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH SLC9A3,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Embryo;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9831664; DOI=10.1016/s0378-1119(98)00485-5;
RA Imai K., Sarker A.H., Akiyama K., Ikeda S., Yao M., Tsutsui K.,
RA Shohmori T., Seki S.;
RT "Genomic structure and sequence of a human homologue (NTHL1/NTH1) of
RT Escherichia coli endonuclease III with those of the adjacent parts of TSC2
RT and SLC9A3R2 genes.";
RL Gene 222:287-295(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH ADRB2; P2RY1
RP AND P2YR2.
RC TISSUE=Lung;
RX PubMed=9671706; DOI=10.1073/pnas.95.15.8496;
RA Hall R.A., Ostedgaard L.S., Premont R.T., Blitzer J.T., Rahman N.,
RA Welsh M.J., Lefkowitz R.J.;
RT "A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor
RT and cystic fibrosis transmembrane conductance regulator determines binding
RT to the Na+/H+ exchanger regulatory factor family of PDZ proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8496-8501(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
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] (ISOFORMS 1 AND 3).
RC TISSUE=Kidney, and Testis;
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 FUNCTION, AND INTERACTION WITH SLC9A3.
RX PubMed=10455146; DOI=10.1074/jbc.274.35.24753;
RA Zizak M., Lamprecht G., Steplock D., Tariq N., Shenolikar S., Donowitz M.,
RA Yun C.H.C., Weinman E.J.;
RT "cAMP-induced phosphorylation and inhibition of Na(+)/H(+) exchanger 3
RT (NHE3) are dependent on the presence but not the phosphorylation of NHE
RT regulatory factor.";
RL J. Biol. Chem. 274:24753-24758(1999).
RN [10]
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 [11]
RP INTERACTION WITH SGK1 AND KCNJ1/ROMK1.
RX PubMed=14623317; DOI=10.1016/j.bbrc.2003.10.037;
RA Palmada M., Embark H.M., Yun C., Bohmer C., Lang F.;
RT "Molecular requirements for the regulation of the renal outer medullary
RT K(+) channel ROMK1 by the serum- and glucocorticoid-inducible kinase
RT SGK1.";
RL Biochem. Biophys. Res. Commun. 311:629-634(2003).
RN [12]
RP INTERACTION WITH LPAR2.
RX PubMed=15143197; DOI=10.1128/mcb.24.11.5069-5079.2004;
RA Oh Y.-S., Jo N.W., Choi J.W., Kim H.S., Seo S.-W., Kang K.-O., Hwang J.-I.,
RA Heo K., Kim S.-H., Kim Y.-H., Kim I.-H., Kim J.H., Banno Y., Ryu S.H.,
RA Suh P.-G.;
RT "NHERF2 specifically interacts with LPA2 receptor and defines the
RT specificity and efficiency of receptor-mediated phospholipase C-beta3
RT activation.";
RL Mol. Cell. Biol. 24:5069-5079(2004).
RN [13]
RP INTERACTION WITH PODXL.
RX PubMed=15642748; DOI=10.1083/jcb.200407072;
RA Meder D., Shevchenko A., Simons K., Fuellekrug J.;
RT "Gp135/podocalyxin and NHERF-2 participate in the formation of a preapical
RT domain during polarization of MDCK cells.";
RL J. Cell Biol. 168:303-313(2005).
RN [14]
RP FUNCTION.
RX PubMed=18829453; DOI=10.1074/jbc.m805534200;
RA He P., Zhang H., Yun C.C.;
RT "IRBIT, inositol 1,4,5-triphosphate (IP3) receptor-binding protein released
RT with IP3, binds Na+/H+ exchanger NHE3 and activates NHE3 activity in
RT response to calcium.";
RL J. Biol. Chem. 283:33544-33553(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183 AND SER-254, AND
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 [16]
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 [17]
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280 AND SER-303, 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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280, AND IDENTIFICATION BY
RP 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 [20]
RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF 310-337 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 [21]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 9-232.
RG Structural genomics consortium (SGC);
RT "The crystal structure of the first and second PDZ domain of human NHERF-2
RT (SLC9A3R2) interacting with a mode 1 PDZ binding motif.";
RL Submitted (JAN-2007) to the PDB data bank.
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 cAMP-mediated phosphorylation and inhibition
CC of SLC9A3 (PubMed:18829453). May also act as scaffold protein in the
CC nucleus. {ECO:0000269|PubMed:10455146, ECO:0000269|PubMed:18829453,
CC ECO:0000269|PubMed:9096337}.
CC -!- SUBUNIT: Homodimer, and heterodimer with SLC9A3R1. Binds PDZK1. Found
CC in a complex with EZR, PODXL and SLC9A3R2 (By similarity). Interacts
CC (via the PDZ domains) with PODXL (via the C-terminal PDZ-binding motif
CC DTHL); interaction is detected in glomerular epithelium cells (By
CC similarity). Binds ADRB2, SLC9A3, P2RY1, P2YR2, SRY, RDX and LPAR2.
CC Interacts with MCC and PODXL. Interacts with SGK1 and KCNJ1/ROMK1.
CC Interacts (via the PDZ domains) with SLC26A6 isoform 4 and isoform 5.
CC {ECO:0000250, ECO:0000269|PubMed:10455146, ECO:0000269|PubMed:12444019,
CC ECO:0000269|PubMed:14623317, ECO:0000269|PubMed:15143197,
CC ECO:0000269|PubMed:15642748, ECO:0000269|PubMed:16615918,
CC ECO:0000269|PubMed:19555689, ECO:0000269|PubMed:9054412,
CC ECO:0000269|PubMed:9096337, ECO:0000269|PubMed:9671706}.
CC -!- INTERACTION:
CC Q15599; P07355: ANXA2; NbExp=6; IntAct=EBI-1149760, EBI-352622;
CC Q15599; P13569: CFTR; NbExp=14; IntAct=EBI-1149760, EBI-349854;
CC Q15599; Q9Y2H0-1: DLGAP4; NbExp=3; IntAct=EBI-1149760, EBI-12000556;
CC Q15599; Q9HBW0: LPAR2; NbExp=2; IntAct=EBI-1149760, EBI-765995;
CC Q15599; P60484: PTEN; NbExp=5; IntAct=EBI-1149760, EBI-696162;
CC Q15599; P40879: SLC26A3; NbExp=5; IntAct=EBI-1149760, EBI-8542350;
CC Q15599; Q15599: SLC9A3R2; NbExp=2; IntAct=EBI-1149760, EBI-1149760;
CC Q15599; Q05066: SRY; NbExp=9; IntAct=EBI-1149760, EBI-464987;
CC Q15599; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-1149760, EBI-3650647;
CC Q15599; O00308: WWP2; NbExp=3; IntAct=EBI-1149760, EBI-743923;
CC Q15599; P46937: YAP1; NbExp=4; IntAct=EBI-1149760, EBI-1044059;
CC Q15599; B7UR60: E2348C_1442; Xeno; NbExp=6; IntAct=EBI-1149760, EBI-25435618;
CC Q15599; B7UIL3: map; Xeno; NbExp=4; IntAct=EBI-1149760, EBI-25435482;
CC Q15599; Q7DB76: map; Xeno; NbExp=2; IntAct=EBI-1149760, EBI-10039068;
CC Q15599; Q9R0W0: mGluR1a; Xeno; NbExp=2; IntAct=EBI-1149760, EBI-8505383;
CC Q15599; Q8X831: nleH1-1; Xeno; NbExp=5; IntAct=EBI-1149760, EBI-16088619;
CC Q15599; P26043: Rdx; Xeno; NbExp=2; IntAct=EBI-1149760, EBI-647737;
CC Q15599; Q05738: Sry; Xeno; NbExp=5; IntAct=EBI-1149760, EBI-7820116;
CC -!- SUBCELLULAR LOCATION: Endomembrane system {ECO:0000269|PubMed:9054412};
CC Peripheral membrane protein {ECO:0000269|PubMed:9054412}. Nucleus
CC {ECO:0000269|PubMed:9054412}. Apical cell membrane {ECO:0000250}.
CC Note=Localizes with EZR and PODXL at the apical cell membrane of
CC glomerular epithelium cells and the sides of the food processes (By
CC similarity). Nuclear, in a punctate pattern. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q15599-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15599-2; Sequence=VSP_009378;
CC Name=3;
CC IsoId=Q15599-3; Sequence=VSP_046849, VSP_046850;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9054412,
CC ECO:0000269|PubMed:9096337}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH14513.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA90511.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U82108; AAB53042.1; -; mRNA.
DR EMBL; Z50150; CAA90511.1; ALT_FRAME; mRNA.
DR EMBL; AF004900; AAC63061.1; -; mRNA.
DR EMBL; AF035771; AAC52090.1; -; mRNA.
DR EMBL; AB014460; BAA32696.1; -; Genomic_DNA.
DR EMBL; AB016243; BAA33216.1; -; Genomic_DNA.
DR EMBL; AC005600; AAC34208.1; -; Genomic_DNA.
DR EMBL; AC093513; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85563.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85564.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85565.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85566.1; -; Genomic_DNA.
DR EMBL; BC014513; AAH14513.2; ALT_INIT; mRNA.
DR EMBL; BC106001; AAI06002.1; -; mRNA.
DR EMBL; BM920873; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS45382.1; -. [Q15599-1]
DR CCDS; CCDS45383.1; -. [Q15599-2]
DR CCDS; CCDS58407.1; -. [Q15599-3]
DR PIR; G01158; G01158.
DR RefSeq; NP_001123484.1; NM_001130012.2. [Q15599-1]
DR RefSeq; NP_001239002.1; NM_001252073.1. [Q15599-3]
DR RefSeq; NP_004776.3; NM_004785.5. [Q15599-2]
DR PDB; 2D11; X-ray; 2.81 A; E/F/G/H=310-337.
DR PDB; 2HE4; X-ray; 1.45 A; A=147-228.
DR PDB; 2OCS; X-ray; 1.50 A; A=9-91.
DR PDB; 4P0C; X-ray; 1.34 A; A=9-90.
DR PDBsum; 2D11; -.
DR PDBsum; 2HE4; -.
DR PDBsum; 2OCS; -.
DR PDBsum; 4P0C; -.
DR AlphaFoldDB; Q15599; -.
DR SMR; Q15599; -.
DR BioGRID; 114754; 170.
DR CORUM; Q15599; -.
DR DIP; DIP-29093N; -.
DR ELM; Q15599; -.
DR IntAct; Q15599; 63.
DR MINT; Q15599; -.
DR STRING; 9606.ENSP00000408005; -.
DR BindingDB; Q15599; -.
DR ChEMBL; CHEMBL4739686; -.
DR TCDB; 8.A.24.1.2; the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family.
DR GlyGen; Q15599; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q15599; -.
DR PhosphoSitePlus; Q15599; -.
DR BioMuta; SLC9A3R2; -.
DR DMDM; 42559433; -.
DR EPD; Q15599; -.
DR jPOST; Q15599; -.
DR MassIVE; Q15599; -.
DR MaxQB; Q15599; -.
DR PaxDb; Q15599; -.
DR PeptideAtlas; Q15599; -.
DR PRIDE; Q15599; -.
DR ProteomicsDB; 12763; -.
DR ProteomicsDB; 42464; -.
DR ProteomicsDB; 60650; -. [Q15599-1]
DR ProteomicsDB; 60651; -. [Q15599-2]
DR Antibodypedia; 943; 267 antibodies from 35 providers.
DR DNASU; 9351; -.
DR Ensembl; ENST00000424542.7; ENSP00000408005.2; ENSG00000065054.14. [Q15599-1]
DR Ensembl; ENST00000432365.6; ENSP00000402857.2; ENSG00000065054.14. [Q15599-2]
DR Ensembl; ENST00000566198.1; ENSP00000456895.1; ENSG00000065054.14. [Q15599-3]
DR GeneID; 9351; -.
DR KEGG; hsa:9351; -.
DR MANE-Select; ENST00000424542.7; ENSP00000408005.2; NM_001130012.3; NP_001123484.1.
DR UCSC; uc002coi.3; human. [Q15599-1]
DR CTD; 9351; -.
DR DisGeNET; 9351; -.
DR GeneCards; SLC9A3R2; -.
DR HGNC; HGNC:11076; SLC9A3R2.
DR HPA; ENSG00000065054; Low tissue specificity.
DR MIM; 606553; gene.
DR neXtProt; NX_Q15599; -.
DR OpenTargets; ENSG00000065054; -.
DR PharmGKB; PA35932; -.
DR VEuPathDB; HostDB:ENSG00000065054; -.
DR eggNOG; KOG3528; Eukaryota.
DR GeneTree; ENSGT00950000182849; -.
DR HOGENOM; CLU_038627_1_0_1; -.
DR InParanoid; Q15599; -.
DR OMA; HFKRRGV; -.
DR OrthoDB; 1149281at2759; -.
DR PhylomeDB; Q15599; -.
DR TreeFam; TF350449; -.
DR PathwayCommons; Q15599; -.
DR SignaLink; Q15599; -.
DR BioGRID-ORCS; 9351; 13 hits in 1084 CRISPR screens.
DR ChiTaRS; SLC9A3R2; human.
DR EvolutionaryTrace; Q15599; -.
DR GenomeRNAi; 9351; -.
DR Pharos; Q15599; Tbio.
DR PRO; PR:Q15599; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q15599; protein.
DR Bgee; ENSG00000065054; Expressed in apex of heart and 99 other tissues.
DR ExpressionAtlas; Q15599; baseline and differential.
DR Genevisible; Q15599; HS.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; IPI:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
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; ISS:ARUK-UCL.
DR GO; GO:0031800; F:type 3 metabotropic glutamate receptor binding; ISS:ARUK-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; IBA:GO_Central.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR Gene3D; 2.30.42.10; -; 2.
DR IDEAL; IID00212; -.
DR InterPro; IPR015098; EBP50_C-term.
DR InterPro; IPR017300; NHERF-1/NHERF-2.
DR InterPro; IPR031197; NHERF-2.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR PANTHER; PTHR14191:SF4; PTHR14191:SF4; 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; Alternative splicing; Cell membrane; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..337
FT /note="Na(+)/H(+) exchange regulatory cofactor NHE-RF2"
FT /id="PRO_0000096805"
FT DOMAIN 11..90
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 150..230
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 107..144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..337
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 254..277
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 307..328
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JHL1"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 254
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JHL1"
FT MOD_RES 280
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..27
FT /note="MAAPEPLRPRLCRLVRGEQGYGFHLHG -> MARSGSATPPARAPGAPPRSP
FT PQRLVQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046849"
FT VAR_SEQ 28..138
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046850"
FT VAR_SEQ 286..296
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9054412"
FT /id="VSP_009378"
FT CONFLICT 51
FT /note="Missing (in Ref. 2; CAA90511)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="D -> Y (in Ref. 8; BM920873)"
FT /evidence="ECO:0000305"
FT CONFLICT 334..336
FT /note="FSN -> LQH (in Ref. 8; BM920873)"
FT /evidence="ECO:0000305"
FT STRAND 10..15
FT /evidence="ECO:0007829|PDB:4P0C"
FT STRAND 23..27
FT /evidence="ECO:0007829|PDB:4P0C"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:4P0C"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:4P0C"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:4P0C"
FT HELIX 69..78
FT /evidence="ECO:0007829|PDB:4P0C"
FT STRAND 82..88
FT /evidence="ECO:0007829|PDB:4P0C"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:2HE4"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:2HE4"
FT STRAND 169..179
FT /evidence="ECO:0007829|PDB:2HE4"
FT HELIX 184..188
FT /evidence="ECO:0007829|PDB:2HE4"
FT STRAND 195..199
FT /evidence="ECO:0007829|PDB:2HE4"
FT HELIX 209..216
FT /evidence="ECO:0007829|PDB:2HE4"
FT STRAND 219..228
FT /evidence="ECO:0007829|PDB:2HE4"
FT HELIX 327..336
FT /evidence="ECO:0007829|PDB:2D11"
SQ SEQUENCE 337 AA; 37414 MW; 4F5D341590D22ED7 CRC64;
MAAPEPLRPR LCRLVRGEQG YGFHLHGEKG RRGQFIRRVE PGSPAEAAAL RAGDRLVEVN
GVNVEGETHH QVVQRIKAVE GQTRLLVVDQ ETDEELRRRQ LTCTEEMAQR GLPPAHDPWE
PKPDWAHTGS HSSEAGKKDV SGPLRELRPR LCHLRKGPQG YGFNLHSDKS RPGQYIRSVD
PGSPAARSGL RAQDRLIEVN GQNVEGLRHA EVVASIKARE DEARLLVVDP ETDEHFKRLR
VTPTEEHVEG PLPSPVTNGT SPAQLNGGSA CSSRSDLPGS DKDTEDGSAW KQDPFQESGL
HLSPTAAEAK EKARAMRVNK RAPQMDWNRK REIFSNF
