NHRF2_RAT
ID NHRF2_RAT Reviewed; 337 AA.
AC Q920G2; Q91Y70;
DT 16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 25-MAY-2022, entry version 129.
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 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], FUNCTION, SUBCELLULAR LOCATION, INTERACTION
RP WITH EZR AND PODXL, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Renal glomerulus;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 23-337, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Liver;
RX PubMed=11124833; DOI=10.1053/jhep.2001.21143;
RA Fouassier L., Duan C.Y., Feranchak A.P., Yun C.H.C., Sutherland E.,
RA Simon F., Fitz J.G., Doctor R.B.;
RT "Ezrin-radixin-moesin-binding phosphoprotein 50 is expressed at the apical
RT membrane of rat liver epithelia.";
RL Hepatology 33:166-176(2001).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186 AND SER-280, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [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 cAMP-mediated phosphorylation and inhibition
CC of SLC9A3. May also act as scaffold protein in the nucleus.
CC {ECO:0000269|PubMed:11457882}.
CC -!- SUBUNIT: Homodimer, and heterodimer with SLC9A3R1. Binds ADRB2, SLC9A3,
CC P2RY1, P2YR2, SRY, RDX, PDZK1 and LPAR2 (By similarity). Found in a
CC complex with EZR, PODXL and SLC9A3R2. Interacts (via the PDZ domains)
CC with PODXL (via the C-terminal PDZ-binding motif DTHL); interaction is
CC detected in glomerular epithelium cells. Interacts with SGK1 and
CC KCNJ1/ROMK1 (By similarity). Interacts (via the PDZ domains) with
CC SLC26A6 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q920G2; O35240: Asic3; NbExp=2; IntAct=EBI-982439, EBI-982374;
CC -!- SUBCELLULAR LOCATION: Endomembrane system; Peripheral membrane protein.
CC Nucleus. Apical cell membrane. Note=Nuclear, in a punctate pattern.
CC Localizes with EZR and PODXL at the apical cell membrane of glomerular
CC epithelium cells and the sides of the food processes.
CC -!- TISSUE SPECIFICITY: Glomerular epithelium cell (podocyte) (at protein
CC level). Detected in liver, bile duct, kidney glomerulus and lung.
CC {ECO:0000269|PubMed:11124833, ECO:0000269|PubMed:11457882}.
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; AF294257; AAK97088.1; -; mRNA.
DR EMBL; AF259898; AAK49392.1; -; mRNA.
DR RefSeq; NP_446263.2; NM_053811.3.
DR AlphaFoldDB; Q920G2; -.
DR SMR; Q920G2; -.
DR BioGRID; 250471; 1.
DR CORUM; Q920G2; -.
DR IntAct; Q920G2; 2.
DR STRING; 10116.ENSRNOP00000004172; -.
DR iPTMnet; Q920G2; -.
DR PhosphoSitePlus; Q920G2; -.
DR PaxDb; Q920G2; -.
DR PRIDE; Q920G2; -.
DR GeneID; 116501; -.
DR KEGG; rno:116501; -.
DR UCSC; RGD:620380; rat.
DR CTD; 9351; -.
DR RGD; 620380; Slc9a3r2.
DR eggNOG; KOG3528; Eukaryota.
DR InParanoid; Q920G2; -.
DR OrthoDB; 880632at2759; -.
DR PhylomeDB; Q920G2; -.
DR PRO; PR:Q920G2; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0032420; C:stereocilium; ISO:RGD.
DR GO; GO:0032421; C:stereocilium bundle; ISO:RGD.
DR GO; GO:0008013; F:beta-catenin binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IPI:RGD.
DR GO; GO:0060090; F:molecular adaptor activity; IMP:RGD.
DR GO; GO:0019902; F:phosphatase binding; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0047485; F:protein N-terminus 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:0048839; P:inner ear development; IEP:RGD.
DR GO; GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; 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; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR Gene3D; 2.30.42.10; -; 2.
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 Cell membrane; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat.
FT CHAIN 1..337
FT /note="Na(+)/H(+) exchange regulatory cofactor NHE-RF2"
FT /id="PRO_0000096808"
FT DOMAIN 11..91
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 127..146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 246..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 278..292
FT /note="Basic and acidic 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:0000250|UniProtKB:Q15599"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 254
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15599"
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:22673903"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15599"
FT CONFLICT 74
FT /note="H -> Q (in Ref. 2; AAK49392)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="H -> Q (in Ref. 2; AAK49392)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 337 AA; 37369 MW; C4B8E6D0CCFDBB0E CRC64;
MAAPESLRPR LCRLVRGEQG YGFHLHGEKG RRGQFIRRVE PGSPAEAAAL RAGDRLVEVN
GVNVEGETHH QVVHRIKAVE GQTQLLVVDK ETDEELCRRQ LTCTEEMAHR GLPPAHNPWE
PKPDWACSGS LGSDTGHKDV NGPPRELRPR LCHLRRGPQG YGFNLHSDKS RPGQYIRSVD
PGSPASLSGL RAQDRLIEVN GQNVEGLRHA EVVARIKAQE DEARLLVVDP ETDEHFKRLR
VVPTEDHVEG PLPSPVTNGT SLAQLNGGSV CSSRSDLPGS EKDNEDGSAW KRDPFQESGL
HLSPTAAEAK EKARATRVNK RAPQMDWNRK REIFSNF
