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Protein

Na(+)/H(+) exchange regulatory cofactor NHE-RF3

Gene

Pdzk1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. May be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades. In complex with SLC9A3R1, may cluster proteins that are functionally dependent in a mutual fashion and modulate the trafficking and the activity of the associated membrane proteins. May play a role in the cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. May potentiate the CFTR chloride channel activity (By similarity). Required for normal cell-surface expression of SCARB1. Plays a role in maintaining normal plasma cholesterol levels via its effects on SCARB1. Plays a role in the normal localization and function of the chloride-anion exchanger SLC26A6 to the plasma membrane in the brush border of the proximal tubule of the kidney. May be involved in the regulation of proximal tubular Na+-dependent inorganic phosphate cotransport therefore playing an important role in tubule function (By similarity). Component of a complex, composed of PDZK1, SYNGAP1, KLHL17 and NMDA receptors. Interacts (via PDZ1 domain) directly with KLHL17; the interaction is important for integrity of actin cytoskeleton structures in neurons.By similarity1 Publication

GO - Molecular functioni

  • protein complex binding Source: RGD
  • scavenger receptor binding Source: RGD

GO - Biological processi

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Na(+)/H(+) exchange regulatory cofactor NHE-RF3
Short name:
NHERF-3
Alternative name(s):
C-terminal-linking and modulating protein
Dietary Pi-regulated RNA-1
Diphor-1
Na(+)/H(+) exchanger regulatory factor 3
Na/Pi cotransporter C-terminal-associated protein 1
Short name:
NaPi-Cap1
PDZ domain-containing protein 1
Sodium-hydrogen exchanger regulatory factor 3
Gene namesi
Name:Pdzk1
Synonyms:Clamp, Diphor1, Nherf3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 2

Organism-specific databases

RGDi70924. Pdzk1.

Subcellular locationi

GO - Cellular componenti

  • apical plasma membrane Source: RGD
  • brush border membrane Source: UniProtKB
  • extracellular exosome Source: Ensembl
  • intracellular Source: GOC
  • membrane raft Source: RGD
  • microvillus membrane Source: RGD
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 523523Na(+)/H(+) exchange regulatory cofactor NHE-RF3PRO_0000058291Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei108 – 1081PhosphoserineCombined sources
Modified residuei148 – 1481PhosphoserineBy similarity
Modified residuei192 – 1921PhosphoserineBy similarity
Modified residuei250 – 2501PhosphoserineBy similarity
Modified residuei334 – 3341PhosphoserineBy similarity
Modified residuei348 – 3481PhosphoserineBy similarity
Modified residuei451 – 4511PhosphothreonineBy similarity
Modified residuei488 – 4881PhosphothreonineBy similarity
Modified residuei492 – 4921PhosphoserineBy similarity
Modified residuei495 – 4951PhosphoserineBy similarity
Modified residuei507 – 5071PhosphothreonineBy similarity
Modified residuei512 – 5121PhosphoserineBy similarity
Modified residuei514 – 5141PhosphoserineBy similarity
Modified residuei515 – 5151PhosphoserineBy similarity
Modified residuei516 – 5161PhosphoserineBy similarity
Modified residuei518 – 5181PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9JJ40.
PRIDEiQ9JJ40.

PTM databases

iPTMnetiQ9JJ40.
PhosphoSiteiQ9JJ40.

Expressioni

Tissue specificityi

Highly expressed in small intestine and kidney, slightly in the liver. Expression was up-regulated when fed on a low inorganic phosphate diet.2 Publications

Gene expression databases

ExpressionAtlasiQ9JJ40. baseline and differential.
GenevisibleiQ9JJ40. RN.

Interactioni

Subunit structurei

Interacts with PDZK1IP1 and ABCC2. Binds to the C-terminal region of SLC26A3. Interacts (via PDZ domains 1 and 3) with SCARB1 (C-terminal domain). Forms a heterodimeric complex with SLC9A3R1. Interacts with AKAP2, BCR, CFTR, SLCO1A1, SLC22A12, SLC22A4, SLC22A5, SLC9A3R2 and SLC17A1. Component of a complex, composed of PDZK1, SYNGAP1, KLHL17 and NMDA receptors. Interacts (via PDZ1 domain) directly with KLHL17; the interaction is important for integrity of actin cytoskeleton structures in neurons. Interacts (via C-terminal PDZ domain) with SLC26A6 (via C-terminal domain). Interacts (via C-terminal PDZ domain) with SLC9A3 (via C-terminal domain). Interacts (via the first PDZ domain) with PTGIR (via non-isoprenylated C-terminus) (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Grin1P354393EBI-7713572,EBI-877897
Klhl17Q8K43010EBI-7713572,EBI-7713653
Shkbp1Q6P7W27EBI-7713572,EBI-7713890From a different organism.
Syngap1Q9QUH66EBI-7713572,EBI-2310349

GO - Molecular functioni

  • protein complex binding Source: RGD
  • scavenger receptor binding Source: RGD

Protein-protein interaction databases

IntActiQ9JJ40. 6 interactions.
MINTiMINT-1893074.
STRINGi10116.ENSRNOP00000000107.

Structurei

3D structure databases

ProteinModelPortaliQ9JJ40.
SMRiQ9JJ40. Positions 1-107, 125-225, 242-331, 372-457.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini9 – 9082PDZ 1PROSITE-ProRule annotationAdd
BLAST
Domaini128 – 21588PDZ 2PROSITE-ProRule annotationAdd
BLAST
Domaini243 – 32381PDZ 3PROSITE-ProRule annotationAdd
BLAST
Domaini378 – 45881PDZ 4PROSITE-ProRule annotationAdd
BLAST

Domaini

The PDZ 2 and 3 domains seem to be involved in the interaction with SLC26A3.By similarity
Interaction with the C-terminus of CFTR could be mediated through independent binding of 1, 3 and 4 domains.
The PDZ 2 and 4 domains do not interact with the C-terminal region of SCARB1.
The PDZ 1 and 3 domains seem to be involved in the interaction with SLCO1A1.By similarity
The PDZ 1 domain interacts with BCR.By similarity

Sequence similaritiesi

Belongs to the NHER family.Curated
Contains 4 PDZ (DHR) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410ITAE. Eukaryota.
ENOG410ZYGE. LUCA.
GeneTreeiENSGT00530000062999.
HOGENOMiHOG000113782.
HOVERGENiHBG082115.
InParanoidiQ9JJ40.
OMAiVENDTHE.
OrthoDBiEOG73V6K7.

Family and domain databases

Gene3Di2.30.42.10. 4 hits.
InterProiIPR001478. PDZ.
[Graphical view]
PfamiPF00595. PDZ. 4 hits.
[Graphical view]
SMARTiSM00228. PDZ. 4 hits.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 4 hits.
PROSITEiPS50106. PDZ. 4 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9JJ40-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASTFNPREC KLSKKEGQNY GFFLRIEKDT DGHLVRVIEE GSPAEKAGLL
60 70 80 90 100
DGDRVLRING VFVDKEEHAQ VVDLVRKSGN SVTLLVLDGD SYEKAVKHQV
110 120 130 140 150
DLKELDQSPR EPALNEKKPD LGMNGGVETC AQPRLCYLVK EGNSFGFSLK
160 170 180 190 200
TIQGKKGVFL TDITPQGVAM KAGVLADDHL IEVNGENVEN ASHEEVVEKV
210 220 230 240 250
TKSGSRIMFL LVDKETARCH SEQKTPFKRE TASLKLLPHQ PRVVVIKKGS
260 270 280 290 300
NGYGFYLRAG PEQKGQIIKD IEPGSPAEAA GLKNNDLVVA VNGESVEALD
310 320 330 340 350
HDGVVEMIRN GGDQTTLLVL DKEADRIYSL ARFSPLLYCQ SQELPNGSVK
360 370 380 390 400
EAPAPISAPL EAPGSATTED VGDHKPKLCR LIKEDDSYGF HLNAIRGQPG
410 420 430 440 450
SFVKEVQQGG PADKAGLENE DIIIEVNGEN VQDEPYDRVV ERIKSSGEHV
460 470 480 490 500
TLLVCGKVAY SYFQAKKIPI LSSLADPLVA GPDAKGETEH DSAESTKDSS
510 520
HPARDRTLSA ASHSSSNSED TVM
Length:523
Mass (Da):56,800
Last modified:August 16, 2005 - v2
Checksum:i949781568960DB01
GO

Sequence cautioni

The sequence AAB66880.1 differs from that shown. Reason: Frameshift at several positions. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti59 – 602NG → KR in AAB66880 (PubMed:9374845).Curated
Sequence conflicti303 – 3031G → S in AAF74985 (PubMed:10829064).Curated
Sequence conflicti364 – 3641G → S (PubMed:9374845).Curated
Sequence conflicti406 – 4061V → D (PubMed:9374845).Curated
Sequence conflicti416 – 4183GLE → WLK in AAB66880 (PubMed:9374845).Curated
Sequence conflicti484 – 4841A → E in AAF74985 (PubMed:10829064).Curated
Sequence conflicti523 – 5231M → I (PubMed:9374845).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013145 mRNA. Translation: AAB66880.1. Sequence problems.
AF116896 mRNA. Translation: AAF74985.1.
BC078788 mRNA. Translation: AAH78788.1.
RefSeqiNP_113900.1. NM_031712.1.
UniGeneiRn.19842.

Genome annotation databases

EnsembliENSRNOT00000000107; ENSRNOP00000000107; ENSRNOG00000000096.
GeneIDi65144.
KEGGirno:65144.
UCSCiRGD:70924. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF013145 mRNA. Translation: AAB66880.1. Sequence problems.
AF116896 mRNA. Translation: AAF74985.1.
BC078788 mRNA. Translation: AAH78788.1.
RefSeqiNP_113900.1. NM_031712.1.
UniGeneiRn.19842.

3D structure databases

ProteinModelPortaliQ9JJ40.
SMRiQ9JJ40. Positions 1-107, 125-225, 242-331, 372-457.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9JJ40. 6 interactions.
MINTiMINT-1893074.
STRINGi10116.ENSRNOP00000000107.

PTM databases

iPTMnetiQ9JJ40.
PhosphoSiteiQ9JJ40.

Proteomic databases

PaxDbiQ9JJ40.
PRIDEiQ9JJ40.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000000107; ENSRNOP00000000107; ENSRNOG00000000096.
GeneIDi65144.
KEGGirno:65144.
UCSCiRGD:70924. rat.

Organism-specific databases

CTDi5174.
RGDi70924. Pdzk1.

Phylogenomic databases

eggNOGiENOG410ITAE. Eukaryota.
ENOG410ZYGE. LUCA.
GeneTreeiENSGT00530000062999.
HOGENOMiHOG000113782.
HOVERGENiHBG082115.
InParanoidiQ9JJ40.
OMAiVENDTHE.
OrthoDBiEOG73V6K7.

Miscellaneous databases

PROiQ9JJ40.

Gene expression databases

ExpressionAtlasiQ9JJ40. baseline and differential.
GenevisibleiQ9JJ40. RN.

Family and domain databases

Gene3Di2.30.42.10. 4 hits.
InterProiIPR001478. PDZ.
[Graphical view]
PfamiPF00595. PDZ. 4 hits.
[Graphical view]
SMARTiSM00228. PDZ. 4 hits.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 4 hits.
PROSITEiPS50106. PDZ. 4 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of a new gene product (diphor-1) regulated by dietary phosphate."
    Custer M., Spindler B., Verrey F., Murer H., Biber J.
    Am. J. Physiol. 273:F801-F806(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
    Tissue: Kidney cortex.
  2. "Identification of a PDZ-domain-containing protein that interacts with the scavenger receptor class B type I."
    Ikemoto M., Arai H., Feng D., Tanaka K., Aoki J., Dohmae N., Takio K., Adachi H., Tsujimoto M., Inoue K.
    Proc. Natl. Acad. Sci. U.S.A. 97:6538-6543(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH SCARB1.
    Strain: Wistar.
    Tissue: Liver.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Kidney.
  4. "Interaction with PDZK1 is required for expression of organic anion transporting protein 1A1 on the hepatocyte surface."
    Wang P., Wang J.J., Xiao Y., Murray J.W., Novikoff P.M., Angeletti R.H., Orr G.A., Lan D., Silver D.L., Wolkoff A.W.
    J. Biol. Chem. 280:30143-30149(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SLCO1A1.
  5. "Interactions between CAP70 and actinfilin are important for integrity of actin cytoskeleton structures in neurons."
    Chen Y., Li M.
    Neuropharmacology 49:1026-1041(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KLHL17.
  6. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-108, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiNHRF3_RAT
AccessioniPrimary (citable) accession number: Q9JJ40
Secondary accession number(s): O35234, Q6AZ21
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: August 16, 2005
Last modified: July 6, 2016
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.