Guanylyl cyclase C (GCC, or GUCY2C; MIM 601330) produces cGMP following the binding of either endogenous ligands or heat-stable enterotoxins secreted by E. coli and other enteric bacteria. Activation of GCC initiates a signaling cascade that leads to phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR; MIM 602421), followed by a net efflux of ions a... See more...

Aliases for PDZD3 Gene

Aliases for PDZD3 Gene

  • PDZ Domain Containing 3 2 3 5
  • IKEPP 2 3 4
  • Natrium-Phosphate Cotransporter IIa C-Terminal-Associated Protein 2 3 4
  • Na/Pi Cotransporter C-Terminal-Associated Protein 2 3 4
  • Na(+)/H(+) Exchange Regulatory Cofactor NHE-RF4 3 4
  • Sodium-Hydrogen Exchanger Regulatory Factor 4 3 4
  • PDZ Domain-Containing Protein 2 3 4
  • PDZ Domain-Containing Protein 3 3 4
  • PDZ Domain Containing 2 2 3
  • NaPi-Cap2 3 4
  • NHERF-4 3 4
  • NHERF4 3 4
  • PDZK2 3 4
  • Intestinal And Kidney Enriched PDZ Protein 3
  • Intestinal And Kidney-Enriched PDZ Protein 4
  • FLJ22756 2
  • PDZD3 5

External Ids for PDZD3 Gene

Previous HGNC Symbols for PDZD3 Gene

  • PDZK2

Previous GeneCards Identifiers for PDZD3 Gene

  • GC11P118559
  • GC11P119056
  • GC11P114995

Summaries for PDZD3 Gene

Entrez Gene Summary for PDZD3 Gene

  • Guanylyl cyclase C (GCC, or GUCY2C; MIM 601330) produces cGMP following the binding of either endogenous ligands or heat-stable enterotoxins secreted by E. coli and other enteric bacteria. Activation of GCC initiates a signaling cascade that leads to phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR; MIM 602421), followed by a net efflux of ions and water into the intestinal lumen. IKEPP is a regulatory protein that associates with GCC and regulates the amount of cGMP produced following receptor stimulation (Scott et al., 2002 [PubMed 11950846]).[supplied by OMIM, Mar 2008]

GeneCards Summary for PDZD3 Gene

PDZD3 (PDZ Domain Containing 3) is a Protein Coding gene. Diseases associated with PDZD3 include Motility-Related Diarrhea and Diarrhea 1, Secretory Chloride, Congenital. Among its related pathways are HIV Life Cycle and Uptake and actions of bacterial toxins. Gene Ontology (GO) annotations related to this gene include protein C-terminus binding and guanylate cyclase inhibitor activity. An important paralog of this gene is PDZK1.

UniProtKB/Swiss-Prot Summary for PDZD3 Gene

  • Acts as a regulatory protein that associates with GUCY2C and negatively modulates its heat-stable enterotoxin-mediated activation (PubMed:11950846). Stimulates SLC9A3 activity in the presence of elevated calcium ions (PubMed:19088451).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for PDZD3 Gene

Genomics for PDZD3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for PDZD3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J119184 Promoter/Enhancer 0.8 EPDnew ENCODE 250.7 +0.2 211 1.6 ZNF341 ZBTB48 RFX1 ZNF652 GLIS1 HNRNPL HSALNG0087628 PDZD3 NLRX1 HSALNG0087629 CCDC153
GH11J119192 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE 9.3 +9.7 9744 8.8 SP1 CEBPA ZNF217 CTCF CEBPB RAD51 SIN3A REST NFATC3 FOXA2 CCDC153 HSALNG0087630 lnc-DPAGT1-1 piR-51667 RNF26 CBL HINFP ARCN1 DPAGT1 TRAPPC4
GH11J119257 Enhancer 0.9 Ensembl ENCODE 11 +78.0 78044 13 TRIM22 SMARCA5 ZNF316 PRDM10 SPI1 NFE2 BHLHE40 BATF CTCF ZBTB33 CBL RNU6-262P NLRX1 PDZD3 ABCG4 HMBS HINFP MFRP C1QTNF5 DPAGT1
GH11J119217 Enhancer 0.7 ENCODE 11.6 +32.9 32877 2 CEBPB EP300 FOSL1 PRDM10 JUND SMARCA4 MAFK EHMT2 ZBTB33 ZSCAN29 HINFP NLRX1 CBL PDZD3 ABCG4 DPAGT1 C2CD2L H2AX HMBS MFRP
GH11J119237 Enhancer 0.8 Ensembl ENCODE 10.8 +51.6 51644 1.8 ZNF316 NFE2 BATF MAFK MAFG JUNB BHLHE40 CEBPB NFE2L2 RUNX3 HINFP CBL C2CD2L RNU6-262P PDZD3 DPAGT1 ABCG4 NLRX1 H2AX HMBS
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around PDZD3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for PDZD3

Top Transcription factor binding sites by QIAGEN in the PDZD3 gene promoter:
  • AP-2alpha
  • AP-2alphaA
  • AP-2beta
  • AP-2gamma
  • ATF-2
  • c-Ets-1
  • c-Jun
  • Elk-1
  • STAT3
  • STAT5A

Genomic Locations for PDZD3 Gene

Latest Assembly
chr11:119,185,457-119,190,223
(GRCh38/hg38)
Size:
4,767 bases
Orientation:
Plus strand

Previous Assembly
chr11:119,056,184-119,060,922
(GRCh37/hg19 by Entrez Gene)
Size:
4,739 bases
Orientation:
Plus strand

chr11:119,056,166-119,060,932
(GRCh37/hg19 by Ensembl)
Size:
4,767 bases
Orientation:
Plus strand

Genomic View for PDZD3 Gene

Genes around PDZD3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PDZD3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PDZD3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PDZD3 Gene

Proteins for PDZD3 Gene

  • Protein details for PDZD3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q86UT5-NHRF4_HUMAN
    Recommended name:
    Na(+)/H(+) exchange regulatory cofactor NHE-RF4
    Protein Accession:
    Q86UT5
    Secondary Accessions:
    • Q8N6R4
    • Q8NAW7
    • Q8NEX7
    • Q9H5Z3

    Protein attributes for PDZD3 Gene

    Size:
    571 amino acids
    Molecular mass:
    61032 Da
    Quaternary structure:
    • Interacts with the C-terminal region of GUCY2C (PubMed:11950846). Interacts with the C-terminal region SLC9A3 and the interactions decrease in response to elevated calcium ion levels (PubMed:19088451). Interacts with the C-terminal region of SLC34A1 (By similarity). Interacts with USP2 isoform 4 (PubMed:26756164).

    Three dimensional structures from OCA and Proteopedia for PDZD3 Gene

    Alternative splice isoforms for PDZD3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PDZD3 Gene

Post-translational modifications for PDZD3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for PDZD3 Gene

Domains & Families for PDZD3 Gene

Gene Families for PDZD3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for PDZD3 Gene

InterPro:
Blocks:
  • PDZ/DHR/GLGF domain
ProtoNet:

Suggested Antigen Peptide Sequences for PDZD3 Gene

GenScript: Design optimal peptide antigens:
  • PDZ domain-containing protein 2 variant 1 (B0YJ61_HUMAN)
  • Sodium-hydrogen exchanger regulatory factor 4 (NHRF4_HUMAN)
genes like me logo Genes that share domains with PDZD3: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for PDZD3 Gene

Function for PDZD3 Gene

Molecular function for PDZD3 Gene

UniProtKB/Swiss-Prot Function:
Acts as a regulatory protein that associates with GUCY2C and negatively modulates its heat-stable enterotoxin-mediated activation (PubMed:11950846). Stimulates SLC9A3 activity in the presence of elevated calcium ions (PubMed:19088451).

Phenotypes From GWAS Catalog for PDZD3 Gene

Gene Ontology (GO) - Molecular Function for PDZD3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 15523054
GO:0008022 protein C-terminus binding IPI 11950846
GO:0008200 ion channel inhibitor activity TAS 11950846
GO:0030251 guanylate cyclase inhibitor activity IDA 11950846
GO:0043495 protein membrane anchor IBA 21873635
genes like me logo Genes that share ontologies with PDZD3: view
genes like me logo Genes that share phenotypes with PDZD3: view

Animal Models for PDZD3 Gene

MGI Knock Outs for PDZD3:
  • Pdzd3 Pdzd3<tm1a(KOMP)Wtsi>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PDZD3

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for PDZD3 Gene

Localization for PDZD3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for PDZD3 Gene

Cell membrane. Peripheral membrane protein. Cytoplasm. Note=Preferentially accumulates at the apical surface and ileal brush border of intestinal epithelial cells (PubMed:11950846, PubMed:19088451). {ECO:0000269 PubMed:11950846, ECO:0000269 PubMed:19088451}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PDZD3 gene
Compartment Confidence
cytosol 5
plasma membrane 4
extracellular 1
cytoskeleton 1
nucleus 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for PDZD3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS 11950846
GO:0005886 plasma membrane IEA --
GO:0005903 brush border IDA 19088451
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with PDZD3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for PDZD3 Gene

Pathways & Interactions for PDZD3 Gene

genes like me logo Genes that share pathways with PDZD3: view

Pathways by source for PDZD3 Gene

Gene Ontology (GO) - Biological Process for PDZD3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport NAS 11950846
GO:0006833 water transport NAS 11950846
GO:0007168 receptor guanylyl cyclase signaling pathway IC 11950846
GO:0009636 response to toxic substance TAS 11950846
GO:0010754 negative regulation of cGMP-mediated signaling IDA 11950846
genes like me logo Genes that share ontologies with PDZD3: view

No data available for SIGNOR curated interactions for PDZD3 Gene

Drugs & Compounds for PDZD3 Gene

No Compound Related Data Available

Transcripts for PDZD3 Gene

mRNA/cDNA for PDZD3 Gene

2 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
14 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for PDZD3

Alternative Splicing Database (ASD) splice patterns (SP) for PDZD3 Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2a · 2b ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7a · 7b · 7c ^ 8a · 8b · 8c ^ 9 ^ 10 ^ 11 ^ 12a · 12b
SP1: - - -
SP2: - - -
SP3: -
SP4: - -
SP5: -
SP6: -
SP7: - - -
SP8: - - - - -
SP9: - -
SP10: -
SP11:

Relevant External Links for PDZD3 Gene

GeneLoc Exon Structure for
PDZD3

Expression for PDZD3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for PDZD3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PDZD3 Gene

This gene is overexpressed in Colon - Transverse (x20.2), Kidney - Cortex (x13.4), and Small Intestine - Terminal Ileum (x13.0).

Protein differential expression in normal tissues from HIPED for PDZD3 Gene

This gene is overexpressed in Heart (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for PDZD3 Gene



Protein tissue co-expression partners for PDZD3 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for PDZD3

SOURCE GeneReport for Unigene cluster for PDZD3 Gene:

Hs.374726

mRNA Expression by UniProt/SwissProt for PDZD3 Gene:

Q86UT5-NHRF4_HUMAN
Tissue specificity: Expressed in kidney and the gastrointestinal tract. Not detected in brain, heart, skeletal muscle or cells of hematopoietic origin.

Evidence on tissue expression from TISSUES for PDZD3 Gene

  • Adrenal gland(5)
  • Eye(5)
  • Heart(5)
  • Intestine(5)
  • Kidney(5)
  • Liver(5)
  • Lung(5)
  • Nervous system(5)
  • Blood(4.7)
genes like me logo Genes that share expression patterns with PDZD3: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for PDZD3 Gene

Orthologs for PDZD3 Gene

This gene was present in the common ancestor of animals.

Orthologs for PDZD3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia PDZD3 30 31
  • 99.08 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia PDZD3 30 31
  • 86.27 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia PDZD3 30 31
  • 86.27 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Pdzd3 30
  • 83.13 (n)
Mouse
(Mus musculus)
Mammalia Pdzd3 30 17 31
  • 82.8 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia PDZD3 31
  • 68 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia PDZD3 31
  • 63 (a)
OneToOne
Chicken
(Gallus gallus)
Aves PDZD3 30 31
  • 59.06 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia PDZD3 31
  • 49 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia pdzd3 30
  • 54.72 (n)
Zebrafish
(Danio rerio)
Actinopterygii pdzd3a 30 31
  • 50.72 (n)
OneToMany
pdzd3b 31
  • 32 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta Sip1 31
  • 23 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 26 (a)
ManyToMany
-- 31
  • 18 (a)
ManyToMany
Species where no ortholog for PDZD3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for PDZD3 Gene

ENSEMBL:
Gene Tree for PDZD3 (if available)
TreeFam:
Gene Tree for PDZD3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for PDZD3: view image

Paralogs for PDZD3 Gene

Paralogs for PDZD3 Gene

(5) SIMAP similar genes for PDZD3 Gene using alignment to 4 proteins:

  • NHRF4_HUMAN
  • B0YJ61_HUMAN
  • E9PPZ1_HUMAN
  • E9PRB0_HUMAN
genes like me logo Genes that share paralogs with PDZD3: view

Variants for PDZD3 Gene

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for PDZD3 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for PDZD3 Gene

Variant ID Type Subtype PubMed ID
nsv468879 CNV loss 19166990
nsv556466 CNV loss 21841781
nsv556467 CNV loss 21841781
nsv556468 CNV loss 21841781

Variation tolerance for PDZD3 Gene

Residual Variation Intolerance Score: 88.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.58; 56.17% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for PDZD3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
PDZD3

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for PDZD3 Gene

Disorders for PDZD3 Gene

MalaCards: The human disease database

(4) MalaCards diseases for PDZD3 Gene - From: COP

- elite association - COSMIC cancer census association via MalaCards
Search PDZD3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for PDZD3

genes like me logo Genes that share disorders with PDZD3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for PDZD3 Gene

Publications for PDZD3 Gene

  1. A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor. (PMID: 11950846) Scott RO … Milgram SL (The Journal of biological chemistry 2002) 2 3 4
  2. USP2-45 Is a Circadian Clock Output Effector Regulating Calcium Absorption at the Post-Translational Level. (PMID: 26756164) Pouly D … Staub O (PloS one 2016) 3 4
  3. Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4) dependent mechanism. (PMID: 19088451) Zachos NC … Donowitz M (Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2008) 3 4
  4. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4

Products for PDZD3 Gene

Sources for PDZD3 Gene