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Protein

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

Gene

PDZK1

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 4 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. 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).By similarity1 Publication

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):
CFTR-associated protein of 70 kDa
Na(+)/H(+) exchanger regulatory factor 3
PDZ domain-containing protein 1
Sodium-hydrogen exchanger regulatory factor 3
Gene namesi
Name:PDZK1
Synonyms:CAP70, NHERF3
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

Subcellular locationi

  • Membrane By similarity; Peripheral membrane protein By similarity
  • Cell membrane By similarity

  • Note: Associated with peripheral membranes. Localizes to the apical compartment of proximal tubular cells and to sinusoidal liver membranes.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 518518Na(+)/H(+) exchange regulatory cofactor NHE-RF3PRO_0000058290Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei108 – 1081PhosphoserineBy similarity
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 residuei507 – 5071PhosphoserineBy similarity
Modified residuei509 – 5091PhosphoserineBy similarity
Modified residuei510 – 5101PhosphoserineBy similarity
Modified residuei511 – 5111PhosphoserineBy similarity
Modified residuei513 – 5131PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Expressioni

Tissue specificityi

Highly expressed in the brush border membrane of duodenal and ileal mucosa.1 Publication

Interactioni

Subunit structurei

Interacts with PDZK1IP1 and ABCC2. 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 SLC9A3 (via C-terminal domain). Interacts (via the first PDZ domain) with PTGIR (via non-isoprenylated C-terminus) (By similarity). Binds to the C-terminal region of SLC26A3. Interacts (via C-terminal PDZ domain) with SLC26A6 (via C-terminal domain).By similarity2 Publications

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000017122.

Structurei

3D structure databases

ProteinModelPortaliQ865P3.
SMRiQ865P3. Positions 1-107, 132-224, 242-331, 376-459.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini9 – 9082PDZ 1PROSITE-ProRule annotationAdd
BLAST
Domaini135 – 21581PDZ 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 PDZ 1, 3 and 4 domains.By similarity
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.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.
HOGENOMiHOG000113782.
HOVERGENiHBG082115.
InParanoidiQ865P3.

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.

Q865P3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASTFNPREC KLSKEEGQNY GFFLRIEKDT EGHLVRVIEK GSPAEKAGLQ
60 70 80 90 100
DGDRVLRING VFVDKEEHMQ VVDLVRKSGN AVTLLVLDGN SYEKAVKKQV
110 120 130 140 150
DLKELGQSRQ EADLRDENVA PVMNGGVETW TQPRLCYLEK QGNSYGFSLK
160 170 180 190 200
TVQGKKGVYM TDIIPQSVAM KAGVLADDHL IEVNGENVED ASHEEVVEKV
210 220 230 240 250
KKSGNRIVFL LVDKETEKRH SEQKIEFRRE AASLKLLPHQ PRIVEMKKGS
260 270 280 290 300
SGYGFYLKAG PEQRGQIIKD IDSGSPAEAA GLKNNDLVIA VNGKSVEALD
310 320 330 340 350
HDGVVELIKK GGDQTSLLVV DKEADSMYRL AHFSPFLYYQ SQELPNGSVT
360 370 380 390 400
EVAAPTPVPP EVSSPDPTEE VEDHKPKLCR LDKGENGYGF HLNAIRGLPG
410 420 430 440 450
SFVKEVQKGS PADLAGLEDE DIIIEVNGVN VLDEPYEKVV DRIQSSGDNV
460 470 480 490 500
TLLVCGKKAY EYFQAKKIPI VSSMALPLAI PADSQGMLAE LEYNLHEAKE
510
RAHSTASNSS SNSEDTEL
Length:518
Mass (Da):56,972
Last modified:June 1, 2003 - v1
Checksum:i4493C0512771D466
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY204473 mRNA. Translation: AAO34667.1.
RefSeqiNP_001075620.1. NM_001082151.2.
UniGeneiOcu.3066.

Genome annotation databases

GeneIDi100008900.
KEGGiocu:100008900.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY204473 mRNA. Translation: AAO34667.1.
RefSeqiNP_001075620.1. NM_001082151.2.
UniGeneiOcu.3066.

3D structure databases

ProteinModelPortaliQ865P3.
SMRiQ865P3. Positions 1-107, 132-224, 242-331, 376-459.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000017122.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100008900.
KEGGiocu:100008900.

Organism-specific databases

CTDi5174.

Phylogenomic databases

eggNOGiENOG410ITAE. Eukaryota.
ENOG410ZYGE. LUCA.
HOGENOMiHOG000113782.
HOVERGENiHBG082115.
InParanoidiQ865P3.

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_RABIT
AccessioniPrimary (citable) accession number: Q865P3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: June 1, 2003
Last modified: March 16, 2016
This is version 70 of the entry and version 1 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.