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Q86UT5 (NHRF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. 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-RF4

Short name=NHERF-4
Alternative name(s):
Intestinal and kidney-enriched PDZ protein
Natrium-phosphate cotransporter IIa C-terminal-associated protein 2
Short name=Na/Pi cotransporter C-terminal-associated protein 2
Short name=NaPi-Cap2
PDZ domain-containing protein 2
PDZ domain-containing protein 3
Sodium-hydrogen exchanger regulatory factor 4
Gene names
Name:PDZD3
Synonyms:IKEPP, NHERF4, PDZK2
ORF Names:DLNB27
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length571 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as a regulatory protein that associates with GUCY2C and negatively modulates its heat-stable enterotoxin-mediated activation. Stimulates SLC9A3 activity in the presence of elevated calcium ions. Ref.1 Ref.6

Subunit structure

Interacts with the C-terminal region of GUCY2C. Interacts with the C-terminal region of SLC34A1. Interacts with the C-terminal region SLC9A3 and the interactions decrease in response to elevated calcium ion levels. Ref.1 Ref.6 UniProtKB Q99MJ6

Subcellular location

Cell membrane; Peripheral membrane protein. Cytoplasm. Note: Preferentially accumulates at the apical surface and ileal brush border of intestinal epithelial cells. Ref.1 Ref.6

Tissue specificity

Expressed in kidney and the gastrointestinal tract. Not detected in brain, heart, skeletal muscle or cells of hematopoietic origin. Ref.1

Sequence similarities

Contains 4 PDZ (DHR) domains.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GUCY2CP250924EBI-8299496,EBI-2816795

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.2 (identifier: Q86UT5-1)

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 Ref.1 (identifier: Q86UT5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: Missing.
     67-105: TRQKLPSTLS...PLFCCPPHPP → MEKAADLQDT...LSLAEDHDPY
Isoform 3 (identifier: Q86UT5-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: Missing.
     67-105: TRQKLPSTLS...PLFCCPPHPP → MEKAADLQDT...LSLAEDHDPY
     272-285: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q86UT5-4)

The sequence of this isoform differs from the canonical sequence as follows:
     355-386: QFLWEVDPGLPAKKAGMQAGDRLVAVAGESVE → EWEPWGRWGKVGLGVGTQAYIHLSVHRRGVPV
     387-571: Missing.
Note: No experimental confirmation available.
Isoform 5 (identifier: Q86UT5-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: Missing.
     67-105: TRQKLPSTLS...PLFCCPPHPP → MEKAADLQDT...LSLAEDHDPY
     287-571: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 571571Na(+)/H(+) exchange regulatory cofactor NHE-RF4
PRO_0000058292

Regions

Domain115 – 19682PDZ 1
Domain223 – 30179PDZ 2
Domain329 – 41284PDZ 3
Domain467 – 54882PDZ 4

Natural variations

Alternative sequence1 – 6666Missing in isoform 2, isoform 3 and isoform 5. Ref.1
VSP_051786
Alternative sequence67 – 10539TRQKL…PPHPP → MEKAADLQDTASLTLKFKFN PKLGIDNPVLSLAEDHDPY in isoform 2, isoform 3 and isoform 5. Ref.1
VSP_051787
Alternative sequence272 – 28514Missing in isoform 3. Ref.1
VSP_051788
Alternative sequence287 – 571285Missing in isoform 5. Ref.1
VSP_051789
Alternative sequence355 – 38632QFLWE…GESVE → EWEPWGRWGKVGLGVGTQAY IHLSVHRRGVPV in isoform 4. Ref.1
VSP_051790
Alternative sequence387 – 571185Missing in isoform 4. Ref.1
VSP_051791

Experimental info

Sequence conflict1121R → P in BAB15474. Ref.3
Sequence conflict1251S → G in BAC03780. Ref.3
Sequence conflict2861L → V in BAB15474. Ref.3
Sequence conflict4381R → Q in BAC76050. Ref.2
Sequence conflict4381R → Q in AAH29042. Ref.5

Secondary structure

............... 571
Helix Strand Turn

Details...

Sequences

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

Last modified October 5, 2010. Version 2.
Checksum: B56CDC91348EE592

FASTA57161,032
        10         20         30         40         50         60 
MVTPSPPGNH SLSLEAPRLH TASDLLGNHS LGLPLITALV GSRDRRGRVF SPVPVPLPTN 

        70         80         90        100        110        120 
PTTQHPTRQK LPSTLSGHRV CQAHGEPVLG LCPLLPLFCC PPHPPDPWSL ERPRFCLLSK 

       130        140        150        160        170        180 
EEGKSFGFHL QQELGRAGHV VCRVDPGTSA QRQGLQEGDR ILAVNNDVVE HEDYAVVVRR 

       190        200        210        220        230        240 
IRASSPRVLL TVLARHAHDV ARAQLGEDAH LCPTLGPGVR PRLCHIVKDE GGFGFSVTHG 

       250        260        270        280        290        300 
NQGPFWLVLS TGGAAERAGV PPGARLLEVN GVSVEKFTHN QLTRKLWQSG QQVTLLVAGP 

       310        320        330        340        350        360 
EVEEQCRQLG LPLAAPLAEG WALPTKPRCL HLEKGPQGFG FLLREEKGLD GRPGQFLWEV 

       370        380        390        400        410        420 
DPGLPAKKAG MQAGDRLVAV AGESVEGLGH EETVSRIQGQ GSCVSLTVVD PEADRFFSMV 

       430        440        450        460        470        480 
RLSPLLFLEN TEAPASPRGS SSASLVETED PSLEDTSVPS VPLGSRQCFL YPGPGGSYGF 

       490        500        510        520        530        540 
RLSCVASGPR LFISQVTPGG SAARAGLQVG DVILEVNGYP VGGQNDLERL QQLPEAEPPL 

       550        560        570 
CLKLAARSLR GLEAWIPPGA AEDWALASDL L 

« Hide

Isoform 2 [UniParc].

Checksum: ACDAE2A896787C5D
Show »

FASTA50554,217
Isoform 3 [UniParc].

Checksum: 46F3C5D292274D56
Show »

FASTA49152,548
Isoform 4 [UniParc].

Checksum: BE18E918ECD4009D
Show »

FASTA38641,888
Isoform 5 [UniParc].

Checksum: 87EC9259F8262E0A
Show »

FASTA22024,105

References

« Hide 'large scale' references
[1]"A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor."
Scott R.O., Thelin W.R., Milgram S.L.
J. Biol. Chem. 277:22934-22941(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH GUCY2C, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Intestinal epithelium.
[2]"Identification of a 500-kb region of common allelic loss in chromosome 11q23 in non-MYCN amplified type of neuroblastoma."
Kubo T., Arai Y., Ohira M., Gamou T., Maeno G., Sakiyama T., Toyoda A., Hattori M., Sakaki Y., Nakagawara A., Ohki M.
Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"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] (ISOFORMS 4 AND 5).
Tissue: Ileal mucosa and Kidney.
[4]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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 3).
[6]"Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4) dependent mechanism."
Zachos N.C., Hodson C., Kovbasnjuk O., Li X., Thelin W.R., Cha B., Milgram S., Donowitz M.
Cell. Physiol. Biochem. 22:693-704(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SLC9A3.
[7]"Crystal structure of the 3rd PDZ domain of intestine- and kidney-enriched PDZ domain IKEPP (PDZD3)."
Structural genomics consortium (SGC)
Submitted (JUL-2011) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 326-415.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY047359 mRNA. Translation: AAL10686.1.
AB094096 mRNA. Translation: BAC76050.1.
AK026409 mRNA. Translation: BAB15474.1.
AK091966 mRNA. Translation: BAC03780.1.
AP002956 Genomic DNA. No translation available.
BC029042 mRNA. Translation: AAH29042.1.
CCDSCCDS53719.1. [Q86UT5-2]
CCDS8417.1. [Q86UT5-3]
RefSeqNP_001161940.1. NM_001168468.1. [Q86UT5-2]
NP_079067.3. NM_024791.3. [Q86UT5-3]
UniGeneHs.374726.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2V90X-ray2.00A/B/C/D/E/F326-415[»]
ProteinModelPortalQ86UT5.
SMRQ86UT5. Positions 113-193, 221-415, 464-545.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122940. 4 interactions.
IntActQ86UT5. 1 interaction.
STRING9606.ENSP00000327107.

PTM databases

PhosphoSiteQ86UT5.

Polymorphism databases

DMDM308153467.

Proteomic databases

PaxDbQ86UT5.
PRIDEQ86UT5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000322712; ENSP00000327107; ENSG00000172367. [Q86UT5-3]
ENST00000355547; ENSP00000347742; ENSG00000172367. [Q86UT5-2]
ENST00000392817; ENSP00000376564; ENSG00000172367. [Q86UT5-1]
ENST00000531114; ENSP00000431164; ENSG00000172367. [Q86UT5-1]
GeneID79849.
KEGGhsa:79849.
UCSCuc001pvz.3. human. [Q86UT5-2]
uc001pwb.3. human. [Q86UT5-1]

Organism-specific databases

CTD79849.
GeneCardsGC11P119056.
H-InvDBHIX0201614.
HGNCHGNC:19891. PDZD3.
HPAHPA040482.
MIM607146. gene.
neXtProtNX_Q86UT5.
PharmGKBPA134911718.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG262468.
HOGENOMHOG000048712.
HOVERGENHBG080760.
InParanoidQ86UT5.
OMAGVRPRLC.
OrthoDBEOG73V6K7.
PhylomeDBQ86UT5.
TreeFamTF350449.

Gene expression databases

ArrayExpressQ86UT5.
BgeeQ86UT5.
CleanExHS_PDZD3.
GenevestigatorQ86UT5.

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

EvolutionaryTraceQ86UT5.
GenomeRNAi79849.
NextBio69555.
PROQ86UT5.
SOURCESearch...

Entry information

Entry nameNHRF4_HUMAN
AccessionPrimary (citable) accession number: Q86UT5
Secondary accession number(s): Q8N6R4 expand/collapse secondary AC list , Q8NAW7, Q8NEX7, Q9H5Z3
Entry history
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: October 5, 2010
Last modified: July 9, 2014
This is version 102 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 11

Human chromosome 11: entries, gene names and cross-references to MIM