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Protein

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

Gene

Pdzk1

Organism
Mus musculus (Mouse)
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 similarity7 Publications

GO - Molecular functioni

GO - Biological processi

  • carnitine transport Source: MGI
  • establishment of protein localization to plasma membrane Source: UniProtKB
  • positive regulation of ion transmembrane transport Source: MGI
  • positive regulation of protein targeting to membrane Source: UniProtKB
  • regulation of anion transport Source: UniProtKB
  • transport Source: MGI
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Na(+)/H(+) exchange regulatory cofactor NHE-RF3
Short name:
NHERF-3
Alternative name(s):
CFTR-associated protein of 70 kDa
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:Cap70, Nherf3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1928901. Pdzk1.

Subcellular locationi

GO - Cellular componenti

  • brush border membrane Source: UniProtKB
  • extracellular exosome Source: MGI
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi14K → A: Impairs interaction of the first PDZ domain with SCARB1. 1 Publication1
Mutagenesisi20Y → A: Disrupts interaction of the first PDZ domain with SCARB1. Abolishes interaction with SCARB1; when associated with A-253. 2 Publications1
Mutagenesisi253Y → A: Disrupts interaction of the third PDZ domain with SCARB1. Abolishes interaction with SCARB1; when associated with A-20. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000582881 – 519Na(+)/H(+) exchange regulatory cofactor NHE-RF3Add BLAST519

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei108PhosphoserineBy similarity1
Modified residuei148PhosphoserineCombined sources1
Modified residuei192PhosphoserineCombined sources1
Modified residuei250PhosphoserineCombined sources1
Modified residuei334PhosphoserineCombined sources1
Modified residuei348PhosphoserineCombined sources1
Modified residuei451PhosphothreonineCombined sources1
Modified residuei488PhosphothreonineCombined sources1
Modified residuei489PhosphoserineCombined sources1
Modified residuei492PhosphoserineCombined sources1
Modified residuei503PhosphothreonineCombined sources1
Modified residuei508PhosphoserineCombined sources1
Modified residuei510PhosphoserineCombined sources1
Modified residuei511PhosphoserineCombined sources1
Modified residuei512PhosphoserineCombined sources1
Modified residuei514PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9JIL4.
PaxDbiQ9JIL4.
PeptideAtlasiQ9JIL4.
PRIDEiQ9JIL4.

PTM databases

iPTMnetiQ9JIL4.
PhosphoSitePlusiQ9JIL4.

Expressioni

Tissue specificityi

Expressed in kidney, liver, small intestine. brain, lung, and testis (at protein level).2 Publications

Gene expression databases

BgeeiENSMUSG00000038298.
CleanExiMM_PDZK1.

Interactioni

Subunit structurei

Interacts with PDZK1IP1 and ABCC2. Binds to the C-terminal region of SLC26A3. Interacts (via C-terminal PDZ domain) with SLC26A6 (via C-terminal domain). Interacts (via C-terminal PDZ domain) with SLC9A3 (via C-terminal domain) (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 similarity). Forms a heterodimeric complex with SLC9A3R1. Interacts with AKAP2, BCR, CFTR, SLCO1A1, SLC22A12, SLC22A4, SLC22A5, SLC26A6, SLC9A3R2 and SLC17A1. Interacts (via the first PDZ domain) with PTGIR (via non-isoprenylated C-terminus). Interacts (via PDZ domains 1 and 3) with SCARB1 (C-terminal domain).By similarity7 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi208488. 2 interactors.
IntActiQ9JIL4. 6 interactors.
MINTiMINT-148595.
STRINGi10090.ENSMUSP00000058936.

Structurei

Secondary structure

1519
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 13Combined sources6
Beta strandi23 – 25Combined sources3
Beta strandi34 – 36Combined sources3
Helixi43 – 46Combined sources4
Beta strandi54 – 58Combined sources5
Beta strandi64 – 66Combined sources3
Helixi68 – 77Combined sources10
Turni78 – 80Combined sources3
Beta strandi81 – 87Combined sources7
Helixi89 – 97Combined sources9
Helixi102 – 104Combined sources3
Beta strandi242 – 247Combined sources6
Beta strandi252 – 254Combined sources3
Beta strandi256 – 259Combined sources4
Beta strandi265 – 269Combined sources5
Helixi276 – 280Combined sources5
Beta strandi286 – 291Combined sources6
Helixi301 – 309Combined sources9
Turni310 – 313Combined sources4
Beta strandi314 – 321Combined sources8
Beta strandi376 – 382Combined sources7
Beta strandi391 – 393Combined sources3
Beta strandi402 – 404Combined sources3
Helixi411 – 414Combined sources4
Beta strandi422 – 426Combined sources5
Helixi436 – 444Combined sources9
Beta strandi448 – 455Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D90NMR-A242-330[»]
2EDZNMR-A1-107[»]
3NGHX-ray1.80A/B7-106[»]
3R68X-ray1.30A238-323[»]
3R69X-ray1.50A/B241-322[»]
4F8KX-ray1.70A/B7-106[»]
4R2ZX-ray1.70A/B375-459[»]
ProteinModelPortaliQ9JIL4.
SMRiQ9JIL4.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9JIL4.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 90PDZ 1PROSITE-ProRule annotationAdd BLAST82
Domaini128 – 215PDZ 2PROSITE-ProRule annotationAdd BLAST88
Domaini243 – 323PDZ 3PROSITE-ProRule annotationAdd BLAST81
Domaini378 – 458PDZ 4PROSITE-ProRule annotationAdd BLAST81

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 PDZ 1, 3 and 4 domains.
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
The PDZ 2 and 4 domains do not interact with the C-terminal region of SCARB1.

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.
HOGENOMiHOG000113782.
HOVERGENiHBG082115.
InParanoidiQ9JIL4.
PhylomeDBiQ9JIL4.
TreeFamiTF350449.

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.

Q9JIL4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASTFNPREC KLSKQEGQNY GFFLRIEKDT DGHLIRVIEE GSPAEKAGLL
60 70 80 90 100
DGDRVLRING VFVDKEEHAQ VVELVRKSGN SVTLLVLDGD SYEKAVKNQV
110 120 130 140 150
DLKELDQSQR EAALNDKKPG PGMNGAVEPC AQPRLCYLVK EGNSFGFSLK
160 170 180 190 200
TIQGKKGVYL TDIMPQGVAM KAGVLADDHL IEVNGENVEN ASHEEVVEKV
210 220 230 240 250
TKSGSRIMFL LVDKETARCH SEQKTQFKRE TASLKLLPHQ PRVVVIKKGS
260 270 280 290 300
NGYGFYLRAG PEQKGQIIKD IEPGSPAEAA GLKNNDLVVA VNGKSVEALD
310 320 330 340 350
HDGVVEMIRK GGDQTTLLVL DKEAESIYSL ARFSPLLYCQ SQELPNGSVK
360 370 380 390 400
EGPAPIPAPL EATGSEPTED AEGHKPKLCR LLKEDDSYGF HLNAIRGQPG
410 420 430 440 450
SFVKEVQQGG PADKAGLENE DVIIEVNGEN VQEEPYDRVV ERIKSSGKHV
460 470 480 490 500
TLLVCGKMAY SYFQAKKIPI VSSMAEPLVA GPDEKGETSA ESEHDAHPAK
510
DRTLSTASHS SSNSEDTEM
Length:519
Mass (Da):56,499
Last modified:October 1, 2000 - v1
Checksum:i681B57F4E237BC28
GO

Sequence cautioni

The sequence AAL84634 differs from that shown. Reason: Frameshift at positions 229 and 261.Curated
The sequence BAC26605 differs from that shown. Reason: Frameshift at position 519. The frameshift causes a read through of the stop codon.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24L → R in AAL84634 (PubMed:11051556).Curated1
Sequence conflicti135L → S in AAL84634 (PubMed:11051556).Curated1
Sequence conflicti162D → N in BAB24493 (PubMed:16141072).Curated1
Sequence conflicti162D → N in BAC26598 (PubMed:16141072).Curated1
Sequence conflicti162D → N in BAC26605 (PubMed:16141072).Curated1
Sequence conflicti162D → N in BAB28007 (PubMed:16141072).Curated1
Sequence conflicti162D → N in BAB29600 (PubMed:16141072).Curated1
Sequence conflicti162D → S in AAL84634 (PubMed:11051556).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF474247 mRNA. Translation: AAL84634.1. Frameshift.
AF220100 mRNA. Translation: AAF73863.1.
AK006269 mRNA. Translation: BAB24493.1.
AK029752 mRNA. Translation: BAC26598.1.
AK029764 mRNA. Translation: BAC26605.1. Frameshift.
AK012070 mRNA. Translation: BAB28007.1.
AK014879 mRNA. Translation: BAB29600.1.
BC013512 mRNA. Translation: AAH13512.1.
CCDSiCCDS17649.1.
RefSeqiNP_001139473.1. NM_001146001.1.
NP_067492.2. NM_021517.2.
XP_006501896.1. XM_006501833.2.
XP_011238480.1. XM_011240178.2.
XP_017175164.1. XM_017319675.1.
UniGeneiMm.489677.

Genome annotation databases

GeneIDi59020.
KEGGimmu:59020.
UCSCiuc008qoi.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF474247 mRNA. Translation: AAL84634.1. Frameshift.
AF220100 mRNA. Translation: AAF73863.1.
AK006269 mRNA. Translation: BAB24493.1.
AK029752 mRNA. Translation: BAC26598.1.
AK029764 mRNA. Translation: BAC26605.1. Frameshift.
AK012070 mRNA. Translation: BAB28007.1.
AK014879 mRNA. Translation: BAB29600.1.
BC013512 mRNA. Translation: AAH13512.1.
CCDSiCCDS17649.1.
RefSeqiNP_001139473.1. NM_001146001.1.
NP_067492.2. NM_021517.2.
XP_006501896.1. XM_006501833.2.
XP_011238480.1. XM_011240178.2.
XP_017175164.1. XM_017319675.1.
UniGeneiMm.489677.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D90NMR-A242-330[»]
2EDZNMR-A1-107[»]
3NGHX-ray1.80A/B7-106[»]
3R68X-ray1.30A238-323[»]
3R69X-ray1.50A/B241-322[»]
4F8KX-ray1.70A/B7-106[»]
4R2ZX-ray1.70A/B375-459[»]
ProteinModelPortaliQ9JIL4.
SMRiQ9JIL4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi208488. 2 interactors.
IntActiQ9JIL4. 6 interactors.
MINTiMINT-148595.
STRINGi10090.ENSMUSP00000058936.

PTM databases

iPTMnetiQ9JIL4.
PhosphoSitePlusiQ9JIL4.

Proteomic databases

MaxQBiQ9JIL4.
PaxDbiQ9JIL4.
PeptideAtlasiQ9JIL4.
PRIDEiQ9JIL4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi59020.
KEGGimmu:59020.
UCSCiuc008qoi.2. mouse.

Organism-specific databases

CTDi5174.
MGIiMGI:1928901. Pdzk1.

Phylogenomic databases

eggNOGiENOG410ITAE. Eukaryota.
ENOG410ZYGE. LUCA.
HOGENOMiHOG000113782.
HOVERGENiHBG082115.
InParanoidiQ9JIL4.
PhylomeDBiQ9JIL4.
TreeFamiTF350449.

Miscellaneous databases

EvolutionaryTraceiQ9JIL4.
PROiQ9JIL4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038298.
CleanExiMM_PDZK1.

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...

Entry informationi

Entry nameiNHRF3_MOUSE
AccessioniPrimary (citable) accession number: Q9JIL4
Secondary accession number(s): Q8CDP5, Q8R4G2, Q9CQ72
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: October 1, 2000
Last modified: November 2, 2016
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Disruption of the gene was not associated with abnormal growth and development or redistribution of interacting proteins. However, a modulation of expression of selective ion channels in the kidney, as well as increased serum cholesterol levels were observed.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.