NHRF3_RAT
ID NHRF3_RAT Reviewed; 523 AA.
AC Q9JJ40; O35234; Q6AZ21;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Na(+)/H(+) exchange regulatory cofactor NHE-RF3;
DE Short=NHERF-3;
DE AltName: Full=C-terminal-linking and modulating protein;
DE AltName: Full=Dietary Pi-regulated RNA-1;
DE AltName: Full=Diphor-1;
DE AltName: Full=Na(+)/H(+) exchanger regulatory factor 3;
DE AltName: Full=Na/Pi cotransporter C-terminal-associated protein 1;
DE Short=NaPi-Cap1;
DE AltName: Full=PDZ domain-containing protein 1;
DE AltName: Full=Sodium-hydrogen exchanger regulatory factor 3;
GN Name=Pdzk1; Synonyms=Clamp, Diphor1, Nherf3;
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, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney cortex;
RX PubMed=9374845; DOI=10.1152/ajprenal.1997.273.5.f801;
RA Custer M., Spindler B., Verrey F., Murer H., Biber J.;
RT "Identification of a new gene product (diphor-1) regulated by dietary
RT phosphate.";
RL Am. J. Physiol. 273:F801-F806(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INTERACTION WITH SCARB1.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=10829064; DOI=10.1073/pnas.100114397;
RA Ikemoto M., Arai H., Feng D., Tanaka K., Aoki J., Dohmae N., Takio K.,
RA Adachi H., Tsujimoto M., Inoue K.;
RT "Identification of a PDZ-domain-containing protein that interacts with the
RT scavenger receptor class B type I.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:6538-6543(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 SLCO1A1.
RX PubMed=15994332; DOI=10.1074/jbc.m503969200;
RA Wang P., Wang J.J., Xiao Y., Murray J.W., Novikoff P.M., Angeletti R.H.,
RA Orr G.A., Lan D., Silver D.L., Wolkoff A.W.;
RT "Interaction with PDZK1 is required for expression of organic anion
RT transporting protein 1A1 on the hepatocyte surface.";
RL J. Biol. Chem. 280:30143-30149(2005).
RN [5]
RP INTERACTION WITH KLHL17.
RX PubMed=16054660; DOI=10.1016/j.neuropharm.2005.05.022;
RA Chen Y., Li M.;
RT "Interactions between CAP70 and actinfilin are important for integrity of
RT actin cytoskeleton structures in neurons.";
RL Neuropharmacology 49:1026-1041(2005).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108, AND IDENTIFICATION BY
RP 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: A scaffold protein that connects plasma membrane proteins and
CC regulatory components, regulating their surface expression in
CC epithelial cells apical domains. May be involved in the coordination of
CC a diverse range of regulatory processes for ion transport and second
CC messenger cascades. In complex with SLC9A3R1, may cluster proteins that
CC are functionally dependent in a mutual fashion and modulate the
CC trafficking and the activity of the associated membrane proteins. May
CC play a role in the cellular mechanisms associated with multidrug
CC resistance through its interaction with ABCC2 and PDZK1IP1. May
CC potentiate the CFTR chloride channel activity (By similarity). Required
CC for normal cell-surface expression of SCARB1. Plays a role in
CC maintaining normal plasma cholesterol levels via its effects on SCARB1.
CC Plays a role in the normal localization and function of the chloride-
CC anion exchanger SLC26A6 to the plasma membrane in the brush border of
CC the proximal tubule of the kidney. May be involved in the regulation of
CC proximal tubular Na(+)-dependent inorganic phosphate cotransport
CC therefore playing an important role in tubule function (By similarity).
CC Component of a complex, composed of PDZK1, SYNGAP1, KLHL17 and NMDA
CC receptors. Interacts (via PDZ1 domain) directly with KLHL17; the
CC interaction is important for integrity of actin cytoskeleton structures
CC in neurons. {ECO:0000250, ECO:0000269|PubMed:9374845}.
CC -!- SUBUNIT: Interacts with PDZK1IP1 and ABCC2. Binds to the C-terminal
CC region of SLC26A3. Interacts (via PDZ domains 1 and 3) with SCARB1 (C-
CC terminal domain). Forms a heterodimeric complex with SLC9A3R1.
CC Interacts with AKAP2, BCR, CFTR, SLCO1A1, SLC22A12, SLC22A4, SLC22A5,
CC SLC9A3R2 and SLC17A1. Component of a complex, composed of PDZK1,
CC SYNGAP1, KLHL17 and NMDA receptors. Interacts (via PDZ1 domain)
CC directly with KLHL17; the interaction is important for integrity of
CC actin cytoskeleton structures in neurons. Interacts (via C-terminal PDZ
CC domain) with SLC26A6 (via C-terminal domain). Interacts (via C-terminal
CC PDZ domain) with SLC9A3 (via C-terminal domain). Interacts (via the
CC first PDZ domain) with PTGIR (via non-isoprenylated C-terminus) (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9JJ40; P35439: Grin1; NbExp=3; IntAct=EBI-7713572, EBI-877897;
CC Q9JJ40; Q8K430: Klhl17; NbExp=10; IntAct=EBI-7713572, EBI-7713653;
CC Q9JJ40; Q9QUH6: Syngap1; NbExp=6; IntAct=EBI-7713572, EBI-2310349;
CC Q9JJ40; Q6P7W2: Shkbp1; Xeno; NbExp=7; IntAct=EBI-7713572, EBI-7713890;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:10829064};
CC Peripheral membrane protein {ECO:0000269|PubMed:10829064}. Cell
CC membrane {ECO:0000250|UniProtKB:Q9JIL4}. Note=Associated with
CC peripheral membranes. Localizes to the apical compartment of proximal
CC tubular cells and to sinusoidal liver membranes.
CC {ECO:0000269|PubMed:10829064}.
CC -!- TISSUE SPECIFICITY: Highly expressed in small intestine and kidney,
CC slightly in the liver. Expression was up-regulated when fed on a low
CC inorganic phosphate diet. {ECO:0000269|PubMed:10829064,
CC ECO:0000269|PubMed:9374845}.
CC -!- DOMAIN: The PDZ 2 and 3 domains seem to be involved in the interaction
CC with SLC26A3. {ECO:0000250}.
CC -!- DOMAIN: Interaction with the C-terminus of CFTR could be mediated
CC through independent binding of 1, 3 and 4 domains.
CC -!- DOMAIN: The PDZ 2 and 4 domains do not interact with the C-terminal
CC region of SCARB1.
CC -!- DOMAIN: The PDZ 1 and 3 domains seem to be involved in the interaction
CC with SLCO1A1. {ECO:0000250}.
CC -!- DOMAIN: The PDZ 1 domain interacts with BCR. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the NHER family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB66880.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF013145; AAB66880.1; ALT_SEQ; mRNA.
DR EMBL; AF116896; AAF74985.1; -; mRNA.
DR EMBL; BC078788; AAH78788.1; -; mRNA.
DR RefSeq; NP_113900.1; NM_031712.1.
DR AlphaFoldDB; Q9JJ40; -.
DR SMR; Q9JJ40; -.
DR IntAct; Q9JJ40; 6.
DR MINT; Q9JJ40; -.
DR STRING; 10116.ENSRNOP00000000107; -.
DR iPTMnet; Q9JJ40; -.
DR PhosphoSitePlus; Q9JJ40; -.
DR PaxDb; Q9JJ40; -.
DR PRIDE; Q9JJ40; -.
DR Ensembl; ENSRNOT00000000107; ENSRNOP00000000107; ENSRNOG00000000096.
DR GeneID; 65144; -.
DR KEGG; rno:65144; -.
DR UCSC; RGD:70924; rat.
DR CTD; 5174; -.
DR RGD; 70924; Pdzk1.
DR eggNOG; KOG3528; Eukaryota.
DR GeneTree; ENSGT00950000182849; -.
DR HOGENOM; CLU_031712_1_0_1; -.
DR InParanoid; Q9JJ40; -.
DR OMA; TSVTFHI; -.
DR OrthoDB; 880632at2759; -.
DR PRO; PR:Q9JJ40; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000000096; Expressed in adult mammalian kidney and 19 other tissues.
DR ExpressionAtlas; Q9JJ40; baseline and differential.
DR Genevisible; Q9JJ40; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0005903; C:brush border; ISO:RGD.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0031528; C:microvillus membrane; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; 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:0005124; F:scavenger receptor binding; IDA:RGD.
DR GO; GO:0015879; P:carnitine transport; ISO:RGD.
DR GO; GO:0030301; P:cholesterol transport; NAS:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0046907; P:intracellular transport; NAS:RGD.
DR GO; GO:1904064; P:positive regulation of cation transmembrane transport; ISO:RGD.
DR GO; GO:0032414; P:positive regulation of ion transmembrane transporter activity; ISO:RGD.
DR GO; GO:1905477; P:positive regulation of protein localization to membrane; ISO:RGD.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0044070; P:regulation of anion transport; ISS:UniProtKB.
DR Gene3D; 2.30.42.10; -; 4.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR Pfam; PF00595; PDZ; 3.
DR Pfam; PF17820; PDZ_6; 1.
DR SMART; SM00228; PDZ; 4.
DR SUPFAM; SSF50156; SSF50156; 4.
DR PROSITE; PS50106; PDZ; 4.
PE 1: Evidence at protein level;
KW Cell membrane; Membrane; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..523
FT /note="Na(+)/H(+) exchange regulatory cofactor NHE-RF3"
FT /id="PRO_0000058291"
FT DOMAIN 9..90
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 128..215
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 243..323
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 378..458
FT /note="PDZ 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 479..523
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 483..504
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 505..523
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 108
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 148
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T2W1"
FT MOD_RES 192
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 348
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 451
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 488
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 495
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 507
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 512
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 514
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 515
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 516
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 518
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT CONFLICT 59..60
FT /note="NG -> KR (in Ref. 1; AAB66880)"
FT /evidence="ECO:0000305"
FT CONFLICT 303
FT /note="G -> S (in Ref. 2; AAF74985)"
FT /evidence="ECO:0000305"
FT CONFLICT 364
FT /note="G -> S (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="V -> D (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 416..418
FT /note="GLE -> WLK (in Ref. 1; AAB66880)"
FT /evidence="ECO:0000305"
FT CONFLICT 484
FT /note="A -> E (in Ref. 2; AAF74985)"
FT /evidence="ECO:0000305"
FT CONFLICT 523
FT /note="M -> I (in Ref. 1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 523 AA; 56800 MW; 949781568960DB01 CRC64;
MASTFNPREC KLSKKEGQNY GFFLRIEKDT DGHLVRVIEE GSPAEKAGLL DGDRVLRING
VFVDKEEHAQ VVDLVRKSGN SVTLLVLDGD SYEKAVKHQV DLKELDQSPR EPALNEKKPD
LGMNGGVETC AQPRLCYLVK EGNSFGFSLK TIQGKKGVFL TDITPQGVAM KAGVLADDHL
IEVNGENVEN ASHEEVVEKV TKSGSRIMFL LVDKETARCH SEQKTPFKRE TASLKLLPHQ
PRVVVIKKGS NGYGFYLRAG PEQKGQIIKD IEPGSPAEAA GLKNNDLVVA VNGESVEALD
HDGVVEMIRN GGDQTTLLVL DKEADRIYSL ARFSPLLYCQ SQELPNGSVK EAPAPISAPL
EAPGSATTED VGDHKPKLCR LIKEDDSYGF HLNAIRGQPG SFVKEVQQGG PADKAGLENE
DIIIEVNGEN VQDEPYDRVV ERIKSSGEHV TLLVCGKVAY SYFQAKKIPI LSSLADPLVA
GPDAKGETEH DSAESTKDSS HPARDRTLSA ASHSSSNSED TVM
