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 27-MAR-2024, entry version 213. DE RecName: Full=Na(+)/H(+) exchange regulatory cofactor NHE-RF2 {ECO:0000305}; 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=NHERF2 {ECO:0000312|HGNC:HGNC:11076}; Synonyms=SLC9A3R2; 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 NHERF1. Binds PDZK1. Found in CC a complex with EZR, PODXL and NHERF2 (By similarity). Interacts (via CC 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=28; IntAct=EBI-1149760, EBI-349854; CC Q15599; Q9Y2H0-1: DLGAP4; NbExp=3; IntAct=EBI-1149760, EBI-12000556; CC Q15599; Q9HBW0: LPAR2; NbExp=3; IntAct=EBI-1149760, EBI-765995; CC Q15599; Q15599: NHERF2; NbExp=2; IntAct=EBI-1149760, EBI-1149760; CC Q15599; P60484: PTEN; NbExp=5; IntAct=EBI-1149760, EBI-696162; CC Q15599; P40879: SLC26A3; NbExp=5; IntAct=EBI-1149760, EBI-8542350; 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; B7UMA0: map; Xeno; NbExp=4; IntAct=EBI-1149760, EBI-2529418; 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 179. DR CORUM; Q15599; -. DR DIP; DIP-29093N; -. DR ELM; Q15599; -. DR IntAct; Q15599; 64. 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 SwissPalm; Q15599; -. DR BioMuta; SLC9A3R2; -. DR DMDM; 42559433; -. DR EPD; Q15599; -. DR jPOST; Q15599; -. DR MassIVE; Q15599; -. DR MaxQB; Q15599; -. DR PaxDb; 9606-ENSP00000408005; -. DR PeptideAtlas; Q15599; -. DR ProteomicsDB; 12763; -. DR ProteomicsDB; 42464; -. DR ProteomicsDB; 60650; -. [Q15599-1] DR ProteomicsDB; 60651; -. [Q15599-2] DR Pumba; Q15599; -. DR Antibodypedia; 943; 287 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 AGR; HGNC:11076; -. DR CTD; 9351; -. DR DisGeNET; 9351; -. DR GeneCards; NHERF2; -. DR HGNC; HGNC:11076; NHERF2. DR HPA; ENSG00000065054; Tissue enhanced (heart). 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; LWEPQPE; -. DR OrthoDB; 2914289at2759; -. DR PhylomeDB; Q15599; -. DR TreeFam; TF350449; -. DR PathwayCommons; Q15599; -. DR SignaLink; Q15599; -. DR SIGNOR; Q15599; -. DR BioGRID-ORCS; 9351; 13 hits in 1162 CRISPR screens. DR ChiTaRS; SLC9A3R2; human. DR EvolutionaryTrace; Q15599; -. DR GenomeRNAi; 9351; -. DR Pharos; Q15599; Tchem. DR PRO; PR:Q15599; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q15599; Protein. DR Bgee; ENSG00000065054; Expressed in apex of heart and 101 other cell types or tissues. DR ExpressionAtlas; Q15599; baseline and differential. 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: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 CDD; cd00992; PDZ_signaling; 2. DR Gene3D; 2.30.42.10; -; 2. DR IDEAL; IID00212; -. DR InterPro; IPR015098; EBP50_C. DR InterPro; IPR017300; NHERF-1/NHERF-2. DR InterPro; IPR001478; PDZ. DR InterPro; IPR036034; PDZ_sf. DR PANTHER; PTHR14191:SF4; NA(+)_H(+) EXCHANGE REGULATORY COFACTOR NHE-RF2; 1. DR PANTHER; PTHR14191; PDZ DOMAIN CONTAINING PROTEIN; 1. DR Pfam; PF09007; EBP50_C; 2. DR Pfam; PF00595; PDZ; 2. DR PIRSF; PIRSF037866; EBP50; 1. DR SMART; SM00228; PDZ; 2. DR SUPFAM; SSF50156; PDZ domain-like; 2. DR PROSITE; PS50106; PDZ; 2. DR Genevisible; Q15599; HS. 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 //