NHRF4_MOUSE
ID NHRF4_MOUSE Reviewed; 498 AA.
AC Q99MJ6; Q8BWE5;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 25-MAY-2022, entry version 145.
DE RecName: Full=Na(+)/H(+) exchange regulatory cofactor NHE-RF4;
DE Short=NHERF-4;
DE AltName: Full=Natrium-phosphate cotransporter IIa C-terminal-associated protein 2;
DE Short=Na/Pi cotransporter C-terminal-associated protein 2;
DE Short=NaPi-Cap2;
DE AltName: Full=PDZ domain-containing protein 2;
DE AltName: Full=PDZ domain-containing protein 3;
DE AltName: Full=Sodium-hydrogen exchanger regulatory factor 4;
GN Name=Pdzd3; Synonyms=Nherf4, Pdzk2;
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] {ECO:0000305, ECO:0000312|EMBL:AAK20865.1}
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SLC34A1, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ {ECO:0000312|EMBL:AAK20865.1};
RC TISSUE=Kidney {ECO:0000312|EMBL:AAK20865.1};
RX PubMed=11099500; DOI=10.1074/jbc.m008745200;
RA Gisler S.M., Stagljar I., Traebert M., Bacic D., Biber J., Murer H.;
RT "Interaction of the type IIa Na/Pi-cotransporter with PDZ proteins.";
RL J. Biol. Chem. 276:9206-9213(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
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 SUBCELLULAR LOCATION.
RX PubMed=19088451; DOI=10.1159/000185553;
RA Zachos N.C., Hodson C., Kovbasnjuk O., Li X., Thelin W.R., Cha B.,
RA Milgram S., Donowitz M.;
RT "Elevated intracellular calcium stimulates NHE3 activity by an IKEPP
RT (NHERF4) dependent mechanism.";
RL Cell. Physiol. Biochem. 22:693-704(2008).
RN [4]
RP FUNCTION, INTERACTION WITH USP2, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=26756164; DOI=10.1371/journal.pone.0145155;
RA Pouly D., Chenaux S., Martin V., Babis M., Koch R., Nagoshi E.,
RA Katanaev V.L., Gachon F., Staub O.;
RT "USP2-45 is a circadian clock output effector regulating calcium absorption
RT at the post-translational level.";
RL PLoS ONE 11:E0145155-E0145155(2016).
CC -!- FUNCTION: Acts as a regulatory protein that associates with GUCY2C and
CC negatively modulates its heat-stable enterotoxin-mediated activation
CC (By similarity). Stimulates SLC9A3 activity in the presence of elevated
CC calcium ions (By similarity). {ECO:0000250|UniProtKB:Q86UT5}.
CC -!- SUBUNIT: Interacts with the C-terminal region of GUCY2C (By
CC similarity). Interacts with C-terminal region of SLC9A3 and the
CC interactions decrease in response to elevated calcium ion levels (By
CC similarity). Interacts with the C-terminal region of SLC34A1
CC (PubMed:11099500). Interacts with USP2 isoform 2 (PubMed:26756164).
CC {ECO:0000250|UniProtKB:Q86UT5, ECO:0000269|PubMed:11099500,
CC ECO:0000269|PubMed:26756164}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:26756164};
CC Peripheral membrane protein {ECO:0000305|PubMed:26756164}. Cytoplasm
CC {ECO:0000269|PubMed:26756164}. Note=In kidney, predominantly localized
CC to the subapical compartment of proximal tubular cells
CC (PubMed:11099500). In intestinal epithelial cells, localizes to the
CC ileal brush border and in a juxtanuclear compartment (PubMed:19088451).
CC Expressed in the membrane, with relatively low expression in the
CC cytoplasm (PubMed:26756164). {ECO:0000269|PubMed:11099500,
CC ECO:0000269|PubMed:19088451, ECO:0000269|PubMed:26756164}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney and small intestine. Not
CC detected in heart, brain, spleen, lung, liver, skeletal muscle or
CC testis. {ECO:0000269|PubMed:11099500}.
CC -!- INDUCTION: Isoform 2: Expressed in a circadian manner in the intestine.
CC {ECO:0000269|PubMed:26756164}.
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DR EMBL; AF334612; AAK20865.1; -; mRNA.
DR EMBL; AK052748; BAC35130.1; -; mRNA.
DR CCDS; CCDS23099.1; -.
DR RefSeq; NP_573489.2; NM_133226.2.
DR AlphaFoldDB; Q99MJ6; -.
DR SMR; Q99MJ6; -.
DR BioGRID; 228423; 1.
DR IntAct; Q99MJ6; 3.
DR MINT; Q99MJ6; -.
DR STRING; 10090.ENSMUSP00000034618; -.
DR iPTMnet; Q99MJ6; -.
DR PhosphoSitePlus; Q99MJ6; -.
DR MaxQB; Q99MJ6; -.
DR PaxDb; Q99MJ6; -.
DR PeptideAtlas; Q99MJ6; -.
DR PRIDE; Q99MJ6; -.
DR DNASU; 170761; -.
DR GeneID; 170761; -.
DR KEGG; mmu:170761; -.
DR UCSC; uc009pch.1; mouse.
DR CTD; 79849; -.
DR MGI; MGI:2429554; Pdzd3.
DR eggNOG; KOG3528; Eukaryota.
DR InParanoid; Q99MJ6; -.
DR OrthoDB; 880632at2759; -.
DR PhylomeDB; Q99MJ6; -.
DR TreeFam; TF350449; -.
DR BioGRID-ORCS; 170761; 0 hits in 71 CRISPR screens.
DR PRO; PR:Q99MJ6; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q99MJ6; protein.
DR GO; GO:0043296; C:apical junction complex; ISO:MGI.
DR GO; GO:0045177; C:apical part of cell; IDA:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0005903; C:brush border; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0030251; F:guanylate cyclase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IBA:GO_Central.
DR GO; GO:1990381; F:ubiquitin-specific protease binding; ISO:MGI.
DR GO; GO:0006811; P:ion transport; IEA:InterPro.
DR GO; GO:0010754; P:negative regulation of cGMP-mediated signaling; ISO:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; IBA:GO_Central.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IEA:InterPro.
DR Gene3D; 2.30.42.10; -; 4.
DR InterPro; IPR031200; NHERF-4.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR PANTHER; PTHR14191:SF20; PTHR14191:SF20; 1.
DR Pfam; PF00595; PDZ; 2.
DR Pfam; PF17820; PDZ_6; 2.
DR SMART; SM00228; PDZ; 4.
DR SUPFAM; SSF50156; SSF50156; 4.
DR PROSITE; PS50106; PDZ; 4.
PE 1: Evidence at protein level;
KW Cytoplasm; Membrane; Reference proteome; Repeat.
FT CHAIN 1..498
FT /note="Na(+)/H(+) exchange regulatory cofactor NHE-RF4"
FT /id="PRO_0000058293"
FT DOMAIN 49..130
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 157..235
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 263..346
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 394..475
FT /note="PDZ 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT CONFLICT 429
FT /note="T -> A (in Ref. 2; BAC35130)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 498 AA; 53525 MW; CD979649B08E475A CRC64;
MEAAADLRDT ALLTLKFKFN PRLGIDNPVL SLAEDQDQSD PWNLHRPRFC LLSKEEEKTF
GFHLQQHLGK ADHVVCRVDP GTSAQRQGLR EGDRILAVNN NIVAHEDHAV VVRYIRASGP
RVLLTVLAQH VHDVARVLQG SDAFLCPTLP SGVRPRLCHV VKDEGGFGFS VTHGSRGPFW
LVLSAGGAAE RAGVPPGARL LEVNGASVEK LTYNQLNRKL WQSGDQVTLL VAGLEVEEQC
HQLGMPLAAP LAEGWALPAK PRCLNIEKGP EGFGFLLREE KGLDGRLGQF LWDVDPGLPA
DKAGMKAGDR LVAVAGESVD GLGHEETVSR IRAQGSCVSL IVVDPEADRF FSMVRLSPLL
FLENTEIAAP PLAETKDLPV EDTVEPSGLA GSCQCFLYPG PGGGYGFRLC CVASGPCLFI
SQVTPGGSTA RAGLQVGDTV LEVNGYPVGG DSELDRLQQL TEAEPPLCLK LGARNPQGLE
AWISLESGED WTLASELL
