NHRF2_MOUSE
ID NHRF2_MOUSE Reviewed; 337 AA.
AC Q9JHL1; Q3TDR3; Q6P074; Q8BGL9; Q8BW05; Q9DCR6;
DT 16-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 163.
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=Octs2;
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ; TISSUE=Blood, and Embryo;
RA Sarker A.H., Akiyama K., Tsutsui K., Seki S.;
RT "cDNA cloning, genomic structure and sequence analysis of the mouse
RT mSlc9a3r2/E3karp/Sip-1/Tka-1/Octs2 gene.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Embryonic heart, Kidney, Small intestine, and Spinal cord;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary gland;
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 [4]
RP INTERACTION WITH PDZK1.
RX PubMed=14531806; DOI=10.1046/j.1523-1755.2003.00266.x;
RA Gisler S.M., Pribanic S., Bacic D., Forrer P., Gantenbein A.,
RA Sabourin L.A., Tsuji A., Zhao Z.-S., Manser E., Biber J., Murer H.;
RT "PDZK1: I. a major scaffolder in brush borders of proximal tubular cells.";
RL Kidney Int. 64:1733-1745(2003).
RN [5]
RP INTERACTION WITH SRY.
RX PubMed=16166090; DOI=10.1074/jbc.m504127200;
RA Thevenet L., Albrecht K.H., Malki S., Berta P., Boizet-Bonhoure B.,
RA Poulat F.;
RT "NHERF2/SIP-1 interacts with mouse SRY via a different mechanism than human
RT SRY.";
RL J. Biol. Chem. 280:38625-38630(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130; SER-269 AND SER-280, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Lung, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer, and heterodimer with SLC9A3R1. Binds PDZK1.
CC Interacts with SRY. Binds ADRB2, SLC9A3, P2RY1, P2YR2, RDX and LPAR2
CC (By similarity). Interacts with MCC (By similarity). Found in a complex
CC with EZR, PODXL and SLC9A3R2 (By similarity). Interacts (via the PDZ
CC domains) with PODXL (via the C-terminal PDZ-binding motif DTHL);
CC interaction is detected in glomerular epithelium cells (By similarity).
CC Interacts with SGK1 and KCNJ1/ROMK1 (By similarity). Interacts (via the
CC PDZ domains) with SLC26A6 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9JHL1; P05622: Pdgfrb; NbExp=2; IntAct=EBI-538451, EBI-1554855;
CC Q9JHL1; O08586: Pten; NbExp=3; IntAct=EBI-538451, EBI-1186266;
CC Q9JHL1; P60484: PTEN; Xeno; NbExp=2; IntAct=EBI-538451, EBI-696162;
CC -!- SUBCELLULAR LOCATION: Endomembrane system {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}. Nucleus {ECO:0000250}. Apical cell
CC membrane {ECO:0000250}. Note=Localizes with EZR and PODXL at the apical
CC cell membrane of glomerular epithelium cells and the sides of the food
CC processes. Nuclear, in a punctate pattern (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JHL1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JHL1-2; Sequence=VSP_009379, VSP_009380;
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DR EMBL; AB026489; BAA97568.1; -; mRNA.
DR EMBL; AB026490; BAA97569.1; -; Genomic_DNA.
DR EMBL; AK002557; BAB22185.1; -; mRNA.
DR EMBL; AK039491; BAC30366.1; -; mRNA.
DR EMBL; AK075813; BAC35980.1; -; mRNA.
DR EMBL; AK084801; BAC39282.1; -; mRNA.
DR EMBL; AK170057; BAE41537.1; -; mRNA.
DR EMBL; BC065778; AAH65778.1; -; mRNA.
DR CCDS; CCDS28488.1; -. [Q9JHL1-1]
DR CCDS; CCDS28489.1; -. [Q9JHL1-2]
DR RefSeq; NP_075542.2; NM_023055.2.
DR RefSeq; NP_075938.2; NM_023449.3.
DR AlphaFoldDB; Q9JHL1; -.
DR SMR; Q9JHL1; -.
DR BioGRID; 211159; 16.
DR IntAct; Q9JHL1; 6.
DR MINT; Q9JHL1; -.
DR STRING; 10090.ENSMUSP00000002572; -.
DR iPTMnet; Q9JHL1; -.
DR PhosphoSitePlus; Q9JHL1; -.
DR jPOST; Q9JHL1; -.
DR MaxQB; Q9JHL1; -.
DR PaxDb; Q9JHL1; -.
DR PeptideAtlas; Q9JHL1; -.
DR PRIDE; Q9JHL1; -.
DR ProteomicsDB; 293554; -. [Q9JHL1-1]
DR ProteomicsDB; 293555; -. [Q9JHL1-2]
DR DNASU; 65962; -.
DR GeneID; 65962; -.
DR KEGG; mmu:65962; -.
DR UCSC; uc008axj.2; mouse. [Q9JHL1-2]
DR UCSC; uc008axk.2; mouse. [Q9JHL1-1]
DR CTD; 9351; -.
DR MGI; MGI:1890662; Slc9a3r2.
DR eggNOG; KOG3528; Eukaryota.
DR InParanoid; Q9JHL1; -.
DR OrthoDB; 880632at2759; -.
DR PhylomeDB; Q9JHL1; -.
DR TreeFam; TF350449; -.
DR BioGRID-ORCS; 65962; 5 hits in 72 CRISPR screens.
DR PRO; PR:Q9JHL1; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9JHL1; protein.
DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0032420; C:stereocilium; IDA:MGI.
DR GO; GO:0032421; C:stereocilium bundle; IDA:MGI.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISO:MGI.
DR GO; GO:0060090; F:molecular adaptor activity; ISO:MGI.
DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; IGI:MGI.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IGI:MGI.
DR GO; GO:0034767; P:positive regulation of ion transmembrane transport; ISO:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; IMP:MGI.
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; 2.
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 Alternative splicing; Cell membrane; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..337
FT /note="Na(+)/H(+) exchange regulatory cofactor NHE-RF2"
FT /id="PRO_0000096806"
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 112..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 242..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:0007744|PubMed:21183079"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15599"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q920G2"
FT MOD_RES 254
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15599"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 280
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 303
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15599"
FT VAR_SEQ 1..111
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_009379"
FT VAR_SEQ 112..138
FT /note="LPPAHNPWEPKPDWACSGSLGSDTGQK -> MARSRTSMLPASAPGAPPVNS
FT QLGLTQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_009380"
FT CONFLICT 4
FT /note="P -> L (in Ref. 2; BAC30366/BAC35980/BAC39282)"
FT /evidence="ECO:0000305"
FT CONFLICT 143
FT /note="P -> S (in Ref. 1; BAA97568/BAA97569 and 2;
FT BAE41537)"
FT /evidence="ECO:0000305"
FT CONFLICT 242
FT /note="V -> I (in Ref. 2; BAC30366/BAC35980/BAC39282 and 3;
FT AAH65778)"
FT /evidence="ECO:0000305"
FT CONFLICT 326
FT /note="D -> A (in Ref. 2; BAB22185)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 337 AA; 37403 MW; A28ED245DE453A5F CRC64;
MAAPESLRPR LCRLVRGEQG YGFHLHGEKG RRGQFIRRVE PGSPAEAAAL RAGDRLVEVN
GVNVEGETHH QVVQRIKAVE GQTQLLVVDK ETDEELCRRQ LTCTEEMAHR GLPPAHNPWE
PKPDWACSGS LGSDTGQKDV NGPPRELRPR LCHLRRGPQG YGFNLHSDKS RPGQYIRSVD
PGSPASHSGL RAQDRLIEVN GQNVEGLRHA EVVARIKAQE DEARLLVVDP ETDEHFKRLR
VVPTEEHVEG PLPSPVTNGT SPAQLNGGSV CSSRSDLPGS EKDNEDGSTW KRDPFQESGL
HLSPTAAEAK EKARATRVNK RAPQMDWNRK REIFSNF
