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Q9JIL4 (NHRF3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 114. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Pdzk1
Synonyms:Cap70, Nherf3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length519 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.6 Ref.7 Ref.8 Ref.11 Ref.12

Subunit structure

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). Ref.1 Ref.5 Ref.6 Ref.7 Ref.11 Ref.12 Ref.13

Subcellular location

Cytoplasm. Membrane; Peripheral membrane protein. Cell membrane. Note: Localized in the brush border membrane of renal proximal tubule cells. Associated with peripheral membranes. Localizes to the apical compartment of proximal cells and to sinusoidal liver membranes. Ref.1 Ref.8

Tissue specificity

Expressed in kidney, liver, small intestine. brain, lung, and testis (at protein level). Ref.1 Ref.2

Domain

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.

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.

Sequence similarities

Belongs to the NHER family.

Contains 4 PDZ (DHR) domains.

Sequence caution

The sequence AAL84634.1 differs from that shown. Reason: Frameshift at positions 229 and 261.

The sequence BAC26605.1 differs from that shown. Reason: Frameshift at position 519. The frameshift causes a read through of the stop codon.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 519519Na(+)/H(+) exchange regulatory cofactor NHE-RF3
PRO_0000058288

Regions

Domain9 – 9082PDZ 1
Domain128 – 21588PDZ 2
Domain243 – 32381PDZ 3
Domain378 – 45881PDZ 4

Amino acid modifications

Modified residue4881Phosphothreonine Ref.9
Modified residue4891Phosphoserine Ref.9
Modified residue4921Phosphoserine Ref.9
Modified residue5141Phosphoserine Ref.9

Experimental info

Mutagenesis141K → A: Impairs interaction of the first PDZ domain with SCARB1. Ref.11
Mutagenesis201Y → A: Disrupts interaction of the first PDZ domain with SCARB1. Abolishes interaction with SCARB1; when associated with A-253. Ref.11 Ref.12
Mutagenesis2531Y → A: Disrupts interaction of the third PDZ domain with SCARB1. Abolishes interaction with SCARB1; when associated with A-20. Ref.12
Sequence conflict241L → R in AAL84634. Ref.1
Sequence conflict1351L → S in AAL84634. Ref.1
Sequence conflict1621D → N in BAB24493. Ref.3
Sequence conflict1621D → N in BAC26598. Ref.3
Sequence conflict1621D → N in BAC26605. Ref.3
Sequence conflict1621D → N in BAB28007. Ref.3
Sequence conflict1621D → N in BAB29600. Ref.3
Sequence conflict1621D → S in AAL84634. Ref.1

Secondary structure

..................................... 519
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9JIL4 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 681B57F4E237BC28

FASTA51956,499
        10         20         30         40         50         60 
MASTFNPREC KLSKQEGQNY GFFLRIEKDT DGHLIRVIEE GSPAEKAGLL DGDRVLRING 

        70         80         90        100        110        120 
VFVDKEEHAQ VVELVRKSGN SVTLLVLDGD SYEKAVKNQV DLKELDQSQR EAALNDKKPG 

       130        140        150        160        170        180 
PGMNGAVEPC AQPRLCYLVK EGNSFGFSLK TIQGKKGVYL TDIMPQGVAM KAGVLADDHL 

       190        200        210        220        230        240 
IEVNGENVEN ASHEEVVEKV TKSGSRIMFL LVDKETARCH SEQKTQFKRE TASLKLLPHQ 

       250        260        270        280        290        300 
PRVVVIKKGS NGYGFYLRAG PEQKGQIIKD IEPGSPAEAA GLKNNDLVVA VNGKSVEALD 

       310        320        330        340        350        360 
HDGVVEMIRK GGDQTTLLVL DKEAESIYSL ARFSPLLYCQ SQELPNGSVK EGPAPIPAPL 

       370        380        390        400        410        420 
EATGSEPTED AEGHKPKLCR LLKEDDSYGF HLNAIRGQPG SFVKEVQQGG PADKAGLENE 

       430        440        450        460        470        480 
DVIIEVNGEN VQEEPYDRVV ERIKSSGKHV TLLVCGKMAY SYFQAKKIPI VSSMAEPLVA 

       490        500        510 
GPDEKGETSA ESEHDAHPAK DRTLSTASHS SSNSEDTEM 

« Hide

References

« Hide 'large scale' references
[1]"Accessory protein facilitated CFTR-CFTR interaction, a molecular mechanism to potentiate the chloride channel activity."
Wang S., Yue H., Derin R.B., Guggino W.B., Li M.
Cell 103:169-179(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 351-376 AND 467-485, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH CFTR.
[2]"Targeted disruption of the PDZK1 gene by homologous recombination."
Kocher O., Pal R., Roberts M., Cirovic C., Gilchrist A.
Mol. Cell. Biol. 23:1175-1180(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Testis.
[4]"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].
Strain: FVB/N.
Tissue: Kidney.
[5]"Interaction of the type IIa Na/Pi-cotransporter with PDZ proteins."
Gisler S.M., Stagljar I., Traebert M., Bacic D., Biber J., Murer H.
J. Biol. Chem. 276:9206-9213(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLC17A1.
[6]"PDZK1: I. a major scaffolder in brush borders of proximal tubular cells."
Gisler S.M., Pribanic S., Bacic D., Forrer P., Gantenbein A., Sabourin L.A., Tsuji A., Zhao Z.-S., Manser E., Biber J., Murer H.
Kidney Int. 64:1733-1745(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AKAP2; SLC22A12; SLC22A4; SLC26A6; SLC9A3R1; SLC9A3R2 AND PDZK1IP1.
[7]"PDZK1 directly regulates the function of organic cation/carnitine transporter OCTN2."
Kato Y., Sai Y., Yoshida K., Watanabe C., Hirata T., Tsuji A.
Mol. Pharmacol. 67:734-743(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SLC22A5.
[8]"Role of PDZK1 in membrane expression of renal brush border ion exchangers."
Thomson R.B., Wang T., Thomson B.R., Tarrats L., Girardi A., Mentone S., Soleimani M., Kocher O., Aronson P.S.
Proc. Natl. Acad. Sci. U.S.A. 102:13331-13336(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-488; SER-489; SER-492 AND SER-514, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[10]"Solution structure of the third PDZ domain of PDZ domain containing protein 1."
RIKEN structural genomics initiative (RSGI)
Submitted (DEC-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 242-331.
[11]"In vitro and in vivo analysis of the binding of the C terminus of the HDL receptor scavenger receptor class B, type I (SR-BI), to the PDZ1 domain of its adaptor protein PDZK1."
Kocher O., Birrane G., Tsukamoto K., Fenske S., Yesilaltay A., Pal R., Daniels K., Ladias J.A., Krieger M.
J. Biol. Chem. 285:34999-35010(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 7-106, INTERACTION WITH SCARB1, FUNCTION, MUTAGENESIS OF LYS-14 AND TYR-20.
[12]"Identification of the PDZ3 domain of the adaptor protein PDZK1 as a second, physiologically functional binding site for the C terminus of the high density lipoprotein receptor scavenger receptor class B type I."
Kocher O., Birrane G., Yesilaltay A., Shechter S., Pal R., Daniels K., Krieger M.
J. Biol. Chem. 286:25171-25186(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 238-323 IN COMPLEX WITH SCARB1, INTERACTION WITH SCARB1, MUTAGENESIS OF TYR-20 AND TYR-253, FUNCTION.
[13]"Molecular analysis of the prostacyclin receptor's interaction with the PDZ1 domain of its adaptor protein PDZK1."
Birrane G., Mulvaney E.P., Pal R., Kinsella B.T., Kocher O.
PLoS ONE 8:E53819-E53819(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 7-106 IN COMPLEX WITH PTGIR, INTERACTION WITH PTGIR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS17649.1.
RefSeqNP_001139473.1. NM_001146001.1.
NP_067492.2. NM_021517.2.
XP_006501895.1. XM_006501832.1.
XP_006501896.1. XM_006501833.1.
XP_006501897.1. XM_006501834.1.
UniGeneMm.489677.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ9JIL4.
SMRQ9JIL4. Positions 1-107, 125-492.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid208488. 2 interactions.
IntActQ9JIL4. 6 interactions.
MINTMINT-148595.

PTM databases

PhosphoSiteQ9JIL4.

Proteomic databases

MaxQBQ9JIL4.
PaxDbQ9JIL4.
PRIDEQ9JIL4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000058865; ENSMUSP00000058936; ENSMUSG00000038298.
ENSMUST00000107069; ENSMUSP00000102684; ENSMUSG00000038298.
ENSMUST00000107070; ENSMUSP00000102685; ENSMUSG00000038298.
ENSMUST00000153256; ENSMUSP00000118846; ENSMUSG00000038298.
GeneID59020.
KEGGmmu:59020.
UCSCuc008qoi.2. mouse.

Organism-specific databases

CTD5174.
MGIMGI:1928901. Pdzk1.

Phylogenomic databases

eggNOGNOG315208.
GeneTreeENSGT00530000062999.
HOGENOMHOG000113782.
HOVERGENHBG082115.
InParanoidQ9JIL4.
PhylomeDBQ9JIL4.
TreeFamTF350449.

Gene expression databases

ArrayExpressQ9JIL4.
BgeeQ9JIL4.
CleanExMM_PDZK1.
GenevestigatorQ9JIL4.

Family and domain databases

Gene3D2.30.42.10. 4 hits.
InterProIPR001478. PDZ.
[Graphical view]
PfamPF00595. PDZ. 4 hits.
[Graphical view]
SMARTSM00228. PDZ. 4 hits.
[Graphical view]
SUPFAMSSF50156. SSF50156. 4 hits.
PROSITEPS50106. PDZ. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9JIL4.
NextBio314580.
PROQ9JIL4.
SOURCESearch...

Entry information

Entry nameNHRF3_MOUSE
AccessionPrimary (citable) accession number: Q9JIL4
Secondary accession number(s): Q8CDP5, Q8R4G2, Q9CQ72
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot