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Q5T2W1 (NHRF3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·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, PDZD1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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. 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.

Subunit structure

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, 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 the first PDZ domain) with PTGIR (via non-isoprenylated C-terminus) By similarity. Interacts (via C-terminal PDZ domain) with SLC26A6 (via C-terminal domain) By similarity. Interacts (via C-terminal PDZ domain) with SLC9A3 (via C-terminal domain). Ref.1 Ref.5 Ref.7 Ref.8 Ref.9

Subcellular location

Cytoplasm By similarity. Membrane; 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.

Tissue specificity

Expression is limited to epithelial cells. Expressed in the kidney (brush border of proximal tubule), pancreas, liver, and small intestine. Expressed at a lower level in the adrenal cortex, testis and stomach. Overexpressed in breast, renal and lung carcinomas. Ref.1 Ref.5 Ref.6

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 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.

The PDZ 2 and 4 domains do not interact with the C-terminal region of SCARB1 By similarity.

Sequence similarities

Belongs to the NHER family.

Contains 4 PDZ (DHR) domains.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityAlternative splicing
   DomainRepeat
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcarnitine transport

Inferred from direct assay PubMed 15523054. Source: BHF-UCL

cell proliferation

Traceable author statement Ref.1. Source: UniProtKB

drug transport

Non-traceable author statement PubMed 16738539. Source: UniProtKB

establishment of protein localization to plasma membrane

Inferred from electronic annotation. Source: Ensembl

positive regulation of ion transmembrane transport

Inferred from direct assay PubMed 15523054. Source: BHF-UCL

positive regulation of protein targeting to membrane

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of anion transport

Inferred from sequence or structural similarity. Source: UniProtKB

transport

Inferred from direct assay PubMed 15523054. Source: BHF-UCL

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: Ensembl

brush border membrane

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

membrane raft

Inferred from electronic annotation. Source: Ensembl

microvillus membrane

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionPDZ domain binding

Inferred from physical interaction PubMed 16236806PubMed 16738539. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 12471024Ref.9PubMed 17990980. Source: UniProtKB

transporter activity

Traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CFTRP135692EBI-349819,EBI-349854

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5T2W1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q5T2W1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     154-264: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 519519Na(+)/H(+) exchange regulatory cofactor NHE-RF3
PRO_0000058287

Regions

Domain9 – 9082PDZ 1
Domain134 – 21582PDZ 2
Domain243 – 32381PDZ 3
Domain378 – 45881PDZ 4

Amino acid modifications

Modified residue4921Phosphoserine By similarity
Modified residue5141Phosphoserine By similarity

Natural variations

Alternative sequence154 – 264111Missing in isoform 2.
VSP_044637

Experimental info

Sequence conflict1951E → K in AAC12264. Ref.1
Sequence conflict2701D → G in BAG60531. Ref.2

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 16, 2005. Version 2.
Checksum: 98BF707F87CD77A6

FASTA51957,129
        10         20         30         40         50         60 
MTSTFNPREC KLSKQEGQNY GFFLRIEKDT EGHLVRVVEK CSPAEKAGLQ DGDRVLRING 

        70         80         90        100        110        120 
VFVDKEEHMQ VVDLVRKSGN SVTLLVLDGD SYEKAVKTRV DLKELGQSQK EQGLSDNILS 

       130        140        150        160        170        180 
PVMNGGVQTW TQPRLCYLVK EGGSYGFSLK TVQGKKGVYM TDITPQGVAM RAGVLADDHL 

       190        200        210        220        230        240 
IEVNGENVED ASHEEVVEKV KKSGSRVMFL LVDKETDKRH VEQKIQFKRE TASLKLLPHQ 

       250        260        270        280        290        300 
PRIVEMKKGS NGYGFYLRAG SEQKGQIIKD IDSGSPAEEA GLKNNDLVVA VNGESVETLD 

       310        320        330        340        350        360 
HDSVVEMIRK GGDQTSLLVV DKETDNMYRL AHFSPFLYYQ SQELPNGSVK EAPAPTPTSL 

       370        380        390        400        410        420 
EVSSPPDTTE EVDHKPKLCR LAKGENGYGF HLNAIRGLPG SFIKEVQKGG PADLAGLEDE 

       430        440        450        460        470        480 
DVIIEVNGVN VLDEPYEKVV DRIQSSGKNV TLLVCGKKAY DYFQAKKIPI VSSLADPLDT 

       490        500        510 
PPDSKEGIVV ESNHDSHMAK ERAHSTASHS SSNSEDTEM 

« Hide

Isoform 2 [UniParc].

Checksum: 6AF5DA3B9EF406E9
Show »

FASTA40844,665

References

« Hide 'large scale' references
[1]"Identification and partial characterization of PDZK1: a novel protein containing PDZ interaction domains."
Kocher O., Comella N., Tognazzi K., Brown L.F.
Lab. Invest. 78:117-125(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH PDZK1IP1.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Kidney.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORM 1).
Tissue: Colon.
[5]"PDZK1, a novel PDZ domain-containing protein up-regulated in carcinomas and mapped to chromosome 1q21, interacts with cMOAT (MRP2), the multidrug resistance-associated protein."
Kocher O., Comella N., Gilchrist A., Pal R., Tognazzi K., Brown L.F., Knoll J.H.
Lab. Invest. 79:1161-1170(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INTERACTION WITH ABCC2.
[6]"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: TISSUE SPECIFICITY.
[7]"Bcr (breakpoint cluster region) protein binds to PDZ-domains of scaffold protein PDZK1 and vesicle coat protein Mint3."
Malmberg E.K., Andersson C.X., Gentzsch M., Chen J.H., Mengos A., Cui L., Hansson G.C., Riordan J.R.
J. Cell Sci. 117:5535-5541(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BCR.
[8]"The CFTR associated protein CAP70 interacts with the apical Cl-/HCO3-exchanger DRA in rabbit small intestinal mucosa."
Rossmann H., Jacob P., Baisch S., Hassoun R., Meier J., Natour D., Yahya K., Yun C., Biber J., Lackner K.J., Fiehn W., Gregor M., Seidler U., Lamprecht G.
Biochemistry 44:4477-4487(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLC26A3.
[9]"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: INTERACTION WITH SLC9A3.
[10]"Solution structure of PDZ domains of PDZ domain containing protein 1."
RIKEN structural genomics initiative (RSGI)
Submitted (FEB-2008) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 132-224 AND 376-458.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF012281 mRNA. Translation: AAC12264.1.
AK298269 mRNA. Translation: BAG60531.1.
AL390725 Genomic DNA. Translation: CAI13715.1.
AL390725 Genomic DNA. Translation: CAI13716.1.
BC006496 mRNA. Translation: AAH06496.1.
BC006518 mRNA. Translation: AAH06518.1.
CCDSCCDS55629.1. [Q5T2W1-2]
CCDS924.1. [Q5T2W1-1]
RefSeqNP_001188254.1. NM_001201325.1. [Q5T2W1-1]
NP_001188255.1. NM_001201326.1. [Q5T2W1-2]
NP_002605.2. NM_002614.4. [Q5T2W1-1]
UniGeneHs.444751.
Hs.732345.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2EEINMR-A132-224[»]
2EEJNMR-A376-458[»]
2VSPX-ray2.60A/B/C/D375-459[»]
3TMHX-ray3.80A/E/I375-459[»]
ProteinModelPortalQ5T2W1.
SMRQ5T2W1. Positions 1-107, 132-357, 375-517.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111200. 25 interactions.
IntActQ5T2W1. 10 interactions.
MINTMINT-4999193.
STRING9606.ENSP00000342143.

PTM databases

PhosphoSiteQ5T2W1.

Polymorphism databases

DMDM73621372.

Proteomic databases

MaxQBQ5T2W1.
PaxDbQ5T2W1.
PRIDEQ5T2W1.

Protocols and materials databases

DNASU5174.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344770; ENSP00000342143; ENSG00000174827. [Q5T2W1-1]
ENST00000417171; ENSP00000394485; ENSG00000174827. [Q5T2W1-1]
ENST00000443667; ENSP00000409291; ENSG00000174827.
ENST00000451928; ENSP00000403422; ENSG00000174827. [Q5T2W1-2]
ENST00000581121; ENSP00000464487; ENSG00000265111. [Q5T2W1-1]
ENST00000582332; ENSP00000462232; ENSG00000265111. [Q5T2W1-2]
ENST00000582503; ENSP00000462094; ENSG00000265111.
ENST00000583035; ENSP00000462520; ENSG00000265111. [Q5T2W1-1]
GeneID5174.
KEGGhsa:5174.
UCSCuc001eon.2. human. [Q5T2W1-1]

Organism-specific databases

CTD5174.
GeneCardsGC01P145726.
H-InvDBHIX0056850.
HIX0178034.
HGNCHGNC:8821. PDZK1.
HPACAB008971.
HPA005755.
HPA006155.
MIM603831. gene.
neXtProtNX_Q5T2W1.
PharmGKBPA33165.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG315208.
HOGENOMHOG000113782.
HOVERGENHBG082115.
InParanoidQ5T2W1.
OMAFNPRECK.
OrthoDBEOG73V6K7.
PhylomeDBQ5T2W1.
TreeFamTF350449.

Gene expression databases

BgeeQ5T2W1.
CleanExHS_PDZK1.
GenevestigatorQ5T2W1.

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

ChiTaRSPDZK1. human.
EvolutionaryTraceQ5T2W1.
GeneWikiPDZK1.
GenomeRNAi5174.
NextBio20022.
PROQ5T2W1.
SOURCESearch...

Entry information

Entry nameNHRF3_HUMAN
AccessionPrimary (citable) accession number: Q5T2W1
Secondary accession number(s): B4DPB9 expand/collapse secondary AC list , E7EU02, O60450, Q5T5P6, Q9BQ41
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: August 16, 2005
Last modified: July 9, 2014
This is version 103 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM