NHRF1_RAT
ID NHRF1_RAT Reviewed; 356 AA.
AC Q9JJ19;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Na(+)/H(+) exchange regulatory cofactor NHE-RF1;
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; Synonyms=Nherf, Nherf1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DIMERIZATION.
RC TISSUE=Liver;
RX PubMed=10859298; DOI=10.1074/jbc.c000092200;
RA Fouassier L., Yun C.H.C., Fitz J.G., Doctor R.B.;
RT "Evidence for ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) self-
RT association through PDZ-PDZ interactions.";
RL J. Biol. Chem. 275:25039-25045(2000).
RN [2]
RP INTERACTION WITH PODXL.
RX PubMed=11457882; DOI=10.1172/jci12539;
RA Takeda T., McQuistan T., Orlando R.A., Farquhar M.G.;
RT "Loss of glomerular foot processes is associated with uncoupling of
RT podocalyxin from the actin cytoskeleton.";
RL J. Clin. Invest. 108:289-301(2001).
RN [3]
RP INTERACTION WITH SLC4A7.
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16396499; DOI=10.1021/pr0503073;
RA Moser K., White F.M.;
RT "Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-
RT MS/MS.";
RL J. Proteome Res. 5:98-104(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-277; SER-287; SER-288;
RP THR-290; SER-291 AND SER-299, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. Involved in sperm capacitation. May participate
CC in the regulation of the chloride and bicarbonate homeostasis in
CC spermatozoa. May enhance Wnt signaling. May participate in HTR4
CC targeting to microvilli (By similarity). Involved in the regulation of
CC phosphate reabsorption in the renal proximal tubules (By similarity).
CC {ECO:0000250}.
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 (By similarity). Interacts (via PDZ
CC domains) with ACE2 (via PDZ-binding motif); the interaction may enhance
CC ACE2 membrane residence (By similarity). {ECO:0000250|UniProtKB:O14745,
CC ECO:0000250|UniProtKB:P70441}.
CC -!- INTERACTION:
CC Q9JJ19; O35240: Asic3; NbExp=5; IntAct=EBI-982391, EBI-982374;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Apical cell membrane
CC {ECO:0000250}. Cell projection, filopodium {ECO:0000250}. Cell
CC projection, ruffle {ECO:0000250}. Cell projection, microvillus
CC {ECO:0000250}. Endomembrane system {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Note=Colocalizes with actin in microvilli-rich
CC apical regions of the syncytiotrophoblast. Present in lipid rafts of T-
CC cells. Translocates from the cytoplasm to the apical cell membrane in a
CC PODXL-dependent manner. Colocalizes with CFTR at the midpiece of sperm
CC tail (By similarity). {ECO:0000250}.
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DR EMBL; AF154336; AAF73258.1; -; mRNA.
DR RefSeq; NP_067605.1; NM_021594.1.
DR AlphaFoldDB; Q9JJ19; -.
DR SMR; Q9JJ19; -.
DR BioGRID; 248735; 3.
DR IntAct; Q9JJ19; 2.
DR STRING; 10116.ENSRNOP00000004351; -.
DR iPTMnet; Q9JJ19; -.
DR PhosphoSitePlus; Q9JJ19; -.
DR SwissPalm; Q9JJ19; -.
DR jPOST; Q9JJ19; -.
DR PaxDb; Q9JJ19; -.
DR PRIDE; Q9JJ19; -.
DR Ensembl; ENSRNOT00000004351; ENSRNOP00000004351; ENSRNOG00000003232.
DR GeneID; 59114; -.
DR KEGG; rno:59114; -.
DR CTD; 9368; -.
DR RGD; 708538; Slc9a3r1.
DR eggNOG; KOG3528; Eukaryota.
DR GeneTree; ENSGT00950000182849; -.
DR HOGENOM; CLU_038627_1_0_1; -.
DR InParanoid; Q9JJ19; -.
DR OMA; NGQIHGH; -.
DR OrthoDB; 880632at2759; -.
DR PhylomeDB; Q9JJ19; -.
DR TreeFam; TF350449; -.
DR PRO; PR:Q9JJ19; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000003232; Expressed in jejunum and 20 other tissues.
DR Genevisible; Q9JJ19; RN.
DR GO; GO:0045177; C:apical part of cell; ISO:RGD.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0031526; C:brush border membrane; ISO:RGD.
DR GO; GO:0071944; C:cell periphery; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:GOC.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005902; C:microvillus; ISO:RGD.
DR GO; GO:0031528; C:microvillus membrane; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0098797; C:plasma membrane protein complex; IPI:ARUK-UCL.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0097225; C:sperm midpiece; ISS:UniProtKB.
DR GO; GO:0032420; C:stereocilium; ISO:RGD.
DR GO; GO:0032426; C:stereocilium tip; ISO:RGD.
DR GO; GO:0031698; F:beta-2 adrenergic receptor binding; ISO:RGD.
DR GO; GO:0008013; F:beta-catenin binding; ISO:RGD.
DR GO; GO:0017081; F:chloride channel regulator activity; ISS:UniProtKB.
DR GO; GO:0050780; F:dopamine receptor binding; ISO:RGD.
DR GO; GO:0070851; F:growth factor receptor binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0060090; F:molecular adaptor activity; IMP:RGD.
DR GO; GO:0045159; F:myosin II binding; IDA:RGD.
DR GO; GO:0030165; F:PDZ domain binding; IPI:RGD.
DR GO; GO:0019902; F:phosphatase binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:RGD.
DR GO; GO:0043621; F:protein self-association; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0031799; F:type 2 metabotropic glutamate receptor binding; ISO:RGD.
DR GO; GO:0031800; F:type 3 metabotropic glutamate receptor binding; ISO:RGD.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISO:RGD.
DR GO; GO:0007191; P:adenylate cyclase-activating dopamine receptor signaling pathway; ISO:RGD.
DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; ISO:RGD.
DR GO; GO:0032782; P:bile acid secretion; ISS:UniProtKB.
DR GO; GO:0030643; P:cellular phosphate ion homeostasis; ISO:RGD.
DR GO; GO:0090660; P:cerebrospinal fluid circulation; ISO:RGD.
DR GO; GO:0044782; P:cilium organization; ISO:RGD.
DR GO; GO:0045198; P:establishment of epithelial cell apical/basal polarity; ISO:RGD.
DR GO; GO:0051683; P:establishment of Golgi localization; ISO:RGD.
DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl.
DR GO; GO:0051939; P:gamma-aminobutyric acid import; IGI:ARUK-UCL.
DR GO; GO:0022612; P:gland morphogenesis; ISO:RGD.
DR GO; GO:0034635; P:glutathione transport; ISS:UniProtKB.
DR GO; GO:0098739; P:import across plasma membrane; IGI:ARUK-UCL.
DR GO; GO:0045199; P:maintenance of epithelial cell apical/basal polarity; ISO:RGD.
DR GO; GO:0030033; P:microvillus assembly; ISO:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD.
DR GO; GO:2000146; P:negative regulation of cell motility; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0010764; P:negative regulation of fibroblast migration; IEA:Ensembl.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0010766; P:negative regulation of sodium ion transport; ISO:RGD.
DR GO; GO:0032416; P:negative regulation of sodium:proton antiporter activity; ISO:RGD.
DR GO; GO:0007097; P:nuclear migration; ISO:RGD.
DR GO; GO:0060158; P:phospholipase C-activating dopamine receptor signaling pathway; ISO:RGD.
DR GO; GO:0007009; P:plasma membrane organization; ISO:RGD.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0034767; P:positive regulation of ion transmembrane transport; IDA:RGD.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0008360; P:regulation of cell shape; ISO:RGD.
DR GO; GO:0008361; P:regulation of cell size; ISO:RGD.
DR GO; GO:0045859; P:regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:1903402; P:regulation of renal phosphate excretion; ISO:RGD.
DR GO; GO:0070293; P:renal absorption; ISS:UniProtKB.
DR GO; GO:0097291; P:renal phosphate ion absorption; ISS:UniProtKB.
DR GO; GO:0003096; P:renal sodium ion transport; ISO:RGD.
DR GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 2.30.42.10; -; 2.
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 Acetylation; Cell membrane; Cell projection; Cytoplasm; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Wnt signaling pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT CHAIN 2..356
FT /note="Na(+)/H(+) exchange regulatory cofactor NHE-RF1"
FT /id="PRO_0000096802"
FT DOMAIN 14..94
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 151..231
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 113..142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 265..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 306..320
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 329..346
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 288
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 290
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 356 AA; 38830 MW; C562AEF5870B8E08 CRC64;
MSADAAAGEP LPRLCCLEKG PNGYGFHLHG EKGKVGQFIR LVEPGSPAEK SGLLAGDRLV
EVNGENVEKE THQQVVSRIR AALNAVRLLV VDPETDEQLK KLGVPIREEL LRAQEKSEHT
EPPAAADTKK AGDQNEAEKS HLERCELRPR LCTMKKGPNG YGFNLHSDKS KPGQFIRAVD
PDSPAEASGL RAQDRIVEVN GVCMEGKQHG DVVSAIKAGG DEAKLLVVDK ETDEFFKKCR
VTPSQEHLDG PLPEPFSNGE IQKENSREAL VEPASESPRP ALARSASSDT SEELNAQDSP
KRHDSTEPSS TSSSSDPILD FNISLAVAKE RAHQKRSSKR APQMDWSKKN ELFSNL
