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Protein

Na(+)/H(+) exchange regulatory cofactor NHE-RF4

Gene

PDZD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  • guanylate cyclase inhibitor activity Source: UniProtKB
  • ion channel inhibitor activity Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB

GO - Biological processi

  • cGMP-mediated signaling Source: UniProtKB
  • ion transport Source: UniProtKB
  • negative regulation of cGMP biosynthetic process Source: UniProtKB
  • receptor guanylyl cyclase signaling pathway Source: UniProtKB
  • response to toxic substance Source: UniProtKB
  • water transport Source: UniProtKB
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:PDZD3
Synonyms:IKEPP, NHERF4, PDZK2
ORF Names:DLNB27
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:19891. PDZD3.

Subcellular locationi

GO - Cellular componenti

  • apical part of cell Source: UniProtKB
  • brush border Source: UniProtKB
  • cytosol Source: UniProtKB
  • subapical complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi79849.
OpenTargetsiENSG00000172367.
PharmGKBiPA134911718.

Polymorphism and mutation databases

BioMutaiPDZD3.
DMDMi308153467.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000582921 – 571Na(+)/H(+) exchange regulatory cofactor NHE-RF4Add BLAST571

Proteomic databases

MaxQBiQ86UT5.
PaxDbiQ86UT5.
PeptideAtlasiQ86UT5.
PRIDEiQ86UT5.
TopDownProteomicsiQ86UT5-4. [Q86UT5-4]

PTM databases

iPTMnetiQ86UT5.
PhosphoSitePlusiQ86UT5.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000172367.
CleanExiHS_PDZD3.
ExpressionAtlasiQ86UT5. baseline and differential.
GenevisibleiQ86UT5. HS.

Interactioni

Subunit structurei

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.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ASAP3Q8TDY43EBI-8744528,EBI-2609717
CACNA1SQ136983EBI-8744528,EBI-5329490
GUCY2CP250924EBI-8299496,EBI-2816795
SLC41A3Q96GZ63EBI-8744528,EBI-7225508
SPRYD7Q5W1113EBI-8744528,EBI-10248098

GO - Molecular functioni

  • protein C-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi122940. 8 interactors.
IntActiQ86UT5. 6 interactors.
STRINGi9606.ENSP00000347742.

Structurei

Secondary structure

1571
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi328 – 333Combined sources6
Beta strandi341 – 347Combined sources7
Beta strandi353 – 360Combined sources8
Helixi365 – 368Combined sources4
Beta strandi375 – 380Combined sources6
Helixi390 – 398Combined sources9
Turni399 – 402Combined sources4
Beta strandi403 – 409Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2V90X-ray2.00A/B/C/D/E/F326-415[»]
ProteinModelPortaliQ86UT5.
SMRiQ86UT5.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ86UT5.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini115 – 196PDZ 1PROSITE-ProRule annotationAdd BLAST82
Domaini223 – 301PDZ 2PROSITE-ProRule annotationAdd BLAST79
Domaini329 – 412PDZ 3PROSITE-ProRule annotationAdd BLAST84
Domaini467 – 548PDZ 4PROSITE-ProRule annotationAdd BLAST82

Sequence similaritiesi

Contains 4 PDZ (DHR) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410ITA7. Eukaryota.
ENOG410XURS. LUCA.
GeneTreeiENSGT00530000062999.
HOGENOMiHOG000048712.
HOVERGENiHBG080760.
InParanoidiQ86UT5.
OMAiGVRPRLC.
OrthoDBiEOG091G0KAL.
PhylomeDBiQ86UT5.
TreeFamiTF350449.

Family and domain databases

Gene3Di2.30.42.10. 4 hits.
InterProiIPR031200. NHERF-4.
IPR001478. PDZ.
[Graphical view]
PANTHERiPTHR14191:SF5. PTHR14191:SF5. 1 hit.
PfamiPF00595. PDZ. 4 hits.
[Graphical view]
SMARTiSM00228. PDZ. 4 hits.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 4 hits.
PROSITEiPS50106. PDZ. 4 hits.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q86UT5-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MVTPSPPGNH SLSLEAPRLH TASDLLGNHS LGLPLITALV GSRDRRGRVF
60 70 80 90 100
SPVPVPLPTN PTTQHPTRQK LPSTLSGHRV CQAHGEPVLG LCPLLPLFCC
110 120 130 140 150
PPHPPDPWSL ERPRFCLLSK EEGKSFGFHL QQELGRAGHV VCRVDPGTSA
160 170 180 190 200
QRQGLQEGDR ILAVNNDVVE HEDYAVVVRR IRASSPRVLL TVLARHAHDV
210 220 230 240 250
ARAQLGEDAH LCPTLGPGVR PRLCHIVKDE GGFGFSVTHG NQGPFWLVLS
260 270 280 290 300
TGGAAERAGV PPGARLLEVN GVSVEKFTHN QLTRKLWQSG QQVTLLVAGP
310 320 330 340 350
EVEEQCRQLG LPLAAPLAEG WALPTKPRCL HLEKGPQGFG FLLREEKGLD
360 370 380 390 400
GRPGQFLWEV DPGLPAKKAG MQAGDRLVAV AGESVEGLGH EETVSRIQGQ
410 420 430 440 450
GSCVSLTVVD PEADRFFSMV RLSPLLFLEN TEAPASPRGS SSASLVETED
460 470 480 490 500
PSLEDTSVPS VPLGSRQCFL YPGPGGSYGF RLSCVASGPR LFISQVTPGG
510 520 530 540 550
SAARAGLQVG DVILEVNGYP VGGQNDLERL QQLPEAEPPL CLKLAARSLR
560 570
GLEAWIPPGA AEDWALASDL L
Length:571
Mass (Da):61,032
Last modified:October 5, 2010 - v2
Checksum:iB56CDC91348EE592
GO
Isoform 21 Publication (identifier: Q86UT5-2) [UniParc]FASTAAdd to basket

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

Show »
Length:505
Mass (Da):54,217
Checksum:iACDAE2A896787C5D
GO
Isoform 3Curated (identifier: Q86UT5-3) [UniParc]FASTAAdd to basket

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.Curated
Show »
Length:491
Mass (Da):52,548
Checksum:i46F3C5D292274D56
GO
Isoform 4Curated (identifier: Q86UT5-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     355-386: QFLWEVDPGLPAKKAGMQAGDRLVAVAGESVE → EWEPWGRWGKVGLGVGTQAYIHLSVHRRGVPV
     387-571: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:386
Mass (Da):41,888
Checksum:iBE18E918ECD4009D
GO
Isoform 5Curated (identifier: Q86UT5-5) [UniParc]FASTAAdd to basket

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.Curated
Show »
Length:220
Mass (Da):24,105
Checksum:i87EC9259F8262E0A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti112R → P in BAB15474 (PubMed:14702039).Curated1
Sequence conflicti125S → G in BAC03780 (PubMed:14702039).Curated1
Sequence conflicti286L → V in BAB15474 (PubMed:14702039).Curated1
Sequence conflicti438R → Q in BAC76050 (Ref. 2) Curated1
Sequence conflicti438R → Q in AAH29042 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0517861 – 66Missing in isoform 2, isoform 3 and isoform 5. 3 PublicationsAdd BLAST66
Alternative sequenceiVSP_05178767 – 105TRQKL…PPHPP → MEKAADLQDTASLTLKFKFN PKLGIDNPVLSLAEDHDPY in isoform 2, isoform 3 and isoform 5. 3 PublicationsAdd BLAST39
Alternative sequenceiVSP_051788272 – 285Missing in isoform 3. 2 PublicationsAdd BLAST14
Alternative sequenceiVSP_051789287 – 571Missing in isoform 5. 2 PublicationsAdd BLAST285
Alternative sequenceiVSP_051790355 – 386QFLWE…GESVE → EWEPWGRWGKVGLGVGTQAY IHLSVHRRGVPV in isoform 4. 2 PublicationsAdd BLAST32
Alternative sequenceiVSP_051791387 – 571Missing in isoform 4. 2 PublicationsAdd BLAST185

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS53719.1. [Q86UT5-2]
CCDS8417.1. [Q86UT5-3]
RefSeqiNP_001161940.1. NM_001168468.1. [Q86UT5-2]
NP_079067.3. NM_024791.3. [Q86UT5-3]
XP_011541302.1. XM_011543000.2. [Q86UT5-1]
XP_011541303.1. XM_011543001.2. [Q86UT5-1]
XP_011541304.1. XM_011543002.2. [Q86UT5-1]
UniGeneiHs.374726.

Genome annotation databases

EnsembliENST00000322712; ENSP00000327107; ENSG00000172367. [Q86UT5-3]
ENST00000355547; ENSP00000347742; ENSG00000172367. [Q86UT5-2]
ENST00000531114; ENSP00000431164; ENSG00000172367. [Q86UT5-1]
GeneIDi79849.
KEGGihsa:79849.
UCSCiuc001pvy.4. human. [Q86UT5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS53719.1. [Q86UT5-2]
CCDS8417.1. [Q86UT5-3]
RefSeqiNP_001161940.1. NM_001168468.1. [Q86UT5-2]
NP_079067.3. NM_024791.3. [Q86UT5-3]
XP_011541302.1. XM_011543000.2. [Q86UT5-1]
XP_011541303.1. XM_011543001.2. [Q86UT5-1]
XP_011541304.1. XM_011543002.2. [Q86UT5-1]
UniGeneiHs.374726.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2V90X-ray2.00A/B/C/D/E/F326-415[»]
ProteinModelPortaliQ86UT5.
SMRiQ86UT5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122940. 8 interactors.
IntActiQ86UT5. 6 interactors.
STRINGi9606.ENSP00000347742.

PTM databases

iPTMnetiQ86UT5.
PhosphoSitePlusiQ86UT5.

Polymorphism and mutation databases

BioMutaiPDZD3.
DMDMi308153467.

Proteomic databases

MaxQBiQ86UT5.
PaxDbiQ86UT5.
PeptideAtlasiQ86UT5.
PRIDEiQ86UT5.
TopDownProteomicsiQ86UT5-4. [Q86UT5-4]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000322712; ENSP00000327107; ENSG00000172367. [Q86UT5-3]
ENST00000355547; ENSP00000347742; ENSG00000172367. [Q86UT5-2]
ENST00000531114; ENSP00000431164; ENSG00000172367. [Q86UT5-1]
GeneIDi79849.
KEGGihsa:79849.
UCSCiuc001pvy.4. human. [Q86UT5-1]

Organism-specific databases

CTDi79849.
DisGeNETi79849.
GeneCardsiPDZD3.
H-InvDBHIX0201614.
HGNCiHGNC:19891. PDZD3.
MIMi607146. gene.
neXtProtiNX_Q86UT5.
OpenTargetsiENSG00000172367.
PharmGKBiPA134911718.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ITA7. Eukaryota.
ENOG410XURS. LUCA.
GeneTreeiENSGT00530000062999.
HOGENOMiHOG000048712.
HOVERGENiHBG080760.
InParanoidiQ86UT5.
OMAiGVRPRLC.
OrthoDBiEOG091G0KAL.
PhylomeDBiQ86UT5.
TreeFamiTF350449.

Miscellaneous databases

EvolutionaryTraceiQ86UT5.
GenomeRNAii79849.
PROiQ86UT5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000172367.
CleanExiHS_PDZD3.
ExpressionAtlasiQ86UT5. baseline and differential.
GenevisibleiQ86UT5. HS.

Family and domain databases

Gene3Di2.30.42.10. 4 hits.
InterProiIPR031200. NHERF-4.
IPR001478. PDZ.
[Graphical view]
PANTHERiPTHR14191:SF5. PTHR14191:SF5. 1 hit.
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 nameiNHRF4_HUMAN
AccessioniPrimary (citable) accession number: Q86UT5
Secondary accession number(s): Q8N6R4
, Q8NAW7, Q8NEX7, Q9H5Z3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: October 5, 2010
Last modified: November 30, 2016
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.