This gene encodes a member of the NHERF family of PDZ scaffolding proteins. These proteins mediate many cellular processes by binding to and regulating the membrane expression and protein-protein interactions of membrane receptors and transport proteins. The encoded protein plays a role in intestinal sodium absorption by regulating the activity of the sodium/hydrogen exchanger ... See more...

Aliases for SLC9A3R2 Gene

Aliases for SLC9A3R2 Gene

  • SLC9A3 Regulator 2 2 3 5
  • NHERF-2 2 3 4
  • SIP-1 2 3 4
  • TKA-1 2 3 4
  • Solute Carrier Family 9, Subfamily A (NHE3, Cation Proton Antiporter 3), Member 3 Regulator 2 2 3
  • Solute Carrier Family 9 (Sodium/Hydrogen Exchanger), Isoform 3 Regulatory Factor 2 2 3
  • Solute Carrier Family 9 (Sodium/Hydrogen Exchanger), Isoform 3 Regulator 2 2 3
  • Solute Carrier Family 9 (Sodium/Hydrogen Exchanger), Member 3 Regulator 2 2 3
  • Solute Carrier Family 9 Isoform A3 Regulatory Factor 2 3 4
  • Na(+)/H(+) Exchange Regulatory Cofactor NHE-RF2 3 4
  • NHE3 Kinase A Regulatory Protein E3KARP 3 4
  • Tyrosine Kinase Activator Protein 1 3 4
  • SRY-Interacting Protein 1 3 4
  • E3KARP 2 3
  • NHERF2 3 4
  • Sodium/Hydrogen Exchanger 3 Kinase A Regulatory Protein 3
  • Sodium-Hydrogen Exchanger Regulatory Factor 2 4
  • NHE3 Regulatory Factor 2 3
  • SLC9A3R2 5
  • NHE3RF2 3
  • OCTS2 3
  • SIP1 3

External Ids for SLC9A3R2 Gene

Previous GeneCards Identifiers for SLC9A3R2 Gene

  • GC16P002094
  • GC16P002103
  • GC16P002016
  • GC16P002076
  • GC16P002001
  • GC16P002075
  • GC16P002068
  • GC16P002066
  • GC16P002284
  • GC16P002320
  • GC16P002343
  • GC16P002383
  • GC16P002078
  • GC16P002082
  • GC16P002089
  • GC16P002134
  • GC16P002172
  • GC16P002177
  • GC16P002202
  • GC16P002241

Summaries for SLC9A3R2 Gene

Entrez Gene Summary for SLC9A3R2 Gene

  • This gene encodes a member of the NHERF family of PDZ scaffolding proteins. These proteins mediate many cellular processes by binding to and regulating the membrane expression and protein-protein interactions of membrane receptors and transport proteins. The encoded protein plays a role in intestinal sodium absorption by regulating the activity of the sodium/hydrogen exchanger 3, and may also regulate the cystic fibrosis transmembrane regulator (CFTR) ion channel. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

GeneCards Summary for SLC9A3R2 Gene

SLC9A3R2 (SLC9A3 Regulator 2) is a Protein Coding gene. Diseases associated with SLC9A3R2 include Cystic Fibrosis and Secretory Diarrhea. Among its related pathways are Neuroscience and ADP signalling through P2Y purinoceptor 12. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and beta-catenin binding. An important paralog of this gene is SLC9A3R1.

UniProtKB/Swiss-Prot Summary for SLC9A3R2 Gene

  • Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3 (PubMed:18829453). May also act as scaffold protein in the nucleus.

Gene Wiki entry for SLC9A3R2 Gene

Additional gene information for SLC9A3R2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SLC9A3R2 Gene

Genomics for SLC9A3R2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SLC9A3R2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SLC9A3R2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SLC9A3R2

Top Transcription factor binding sites by QIAGEN in the SLC9A3R2 gene promoter:
  • Egr-3
  • HNF-4alpha1
  • NF-1
  • STAT3

Genomic Locations for SLC9A3R2 Gene

Genomic Locations for SLC9A3R2 Gene
chr16:2,025,356-2,039,026
(GRCh38/hg38)
Size:
13,671 bases
Orientation:
Plus strand
chr16:2,075,357-2,089,027
(GRCh37/hg19)
Size:
13,671 bases
Orientation:
Plus strand

Genomic View for SLC9A3R2 Gene

Genes around SLC9A3R2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SLC9A3R2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SLC9A3R2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SLC9A3R2 Gene

Proteins for SLC9A3R2 Gene

  • Protein details for SLC9A3R2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q15599-NHRF2_HUMAN
    Recommended name:
    Na(+)/H(+) exchange regulatory cofactor NHE-RF2
    Protein Accession:
    Q15599
    Secondary Accessions:
    • D3DU84
    • D3DU85
    • H3BSV6
    • O00272
    • O00556
    • Q3KQY7

    Protein attributes for SLC9A3R2 Gene

    Size:
    337 amino acids
    Molecular mass:
    37414 Da
    Quaternary structure:
    • Homodimer, and heterodimer with SLC9A3R1. Binds PDZK1. Found in a complex with EZR, PODXL and SLC9A3R2 (By similarity). Interacts (via the PDZ domains) with PODXL (via the C-terminal PDZ-binding motif DTHL); interaction is detected in glomerular epithelium cells (By similarity). Binds ADRB2, SLC9A3, P2RY1, P2YR2, SRY, RDX and LPAR2. Interacts with MCC and PODXL. Interacts with SGK1 and KCNJ1/ROMK1. Interacts (via the PDZ domains) with SLC26A6 isoform 4 and isoform 5.
    SequenceCaution:
    • Sequence=AAH14513.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=CAA90511.1; Type=Frameshift; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for SLC9A3R2 Gene

    Alternative splice isoforms for SLC9A3R2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SLC9A3R2 Gene

Post-translational modifications for SLC9A3R2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for SLC9A3R2 Gene

Domains & Families for SLC9A3R2 Gene

Gene Families for SLC9A3R2 Gene

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

Protein Domains for SLC9A3R2 Gene

Suggested Antigen Peptide Sequences for SLC9A3R2 Gene

GenScript: Design optimal peptide antigens:
  • Tyrosine kinase activator protein 1 (NHRF2_HUMAN)
  • SLC9A3R2 protein (Q6NTG0_HUMAN)
genes like me logo Genes that share domains with SLC9A3R2: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for SLC9A3R2 Gene

Function for SLC9A3R2 Gene

Molecular function for SLC9A3R2 Gene

UniProtKB/Swiss-Prot Function:
Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3 (PubMed:18829453). May also act as scaffold protein in the nucleus.

Phenotypes From GWAS Catalog for SLC9A3R2 Gene

Gene Ontology (GO) - Molecular Function for SLC9A3R2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding IPI 16456542
GO:0005515 protein binding IPI 11285285
GO:0008013 beta-catenin binding IPI 17242191
GO:0008022 protein C-terminus binding IPI 11786550
GO:0019902 phosphatase binding IPI 16456542
genes like me logo Genes that share ontologies with SLC9A3R2: view
genes like me logo Genes that share phenotypes with SLC9A3R2: view

Animal Models for SLC9A3R2 Gene

MGI Knock Outs for SLC9A3R2:

Animal Model Products

  • Taconic Biosciences Mouse Models for SLC9A3R2

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SLC9A3R2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SLC9A3R2 Gene

Localization for SLC9A3R2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SLC9A3R2 Gene

Endomembrane system. Peripheral membrane protein. Nucleus. Apical cell membrane. Note=Localizes with EZR and PODXL at the apical cell membrane of glomerular epithelium cells and the sides of the food processes (By similarity). Nuclear, in a punctate pattern. {ECO:0000250}.

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 SLC9A3R2 gene
Compartment Confidence
plasma membrane 5
extracellular 4
nucleus 4
cytoskeleton 2
endosome 2
cytosol 2
mitochondrion 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for SLC9A3R2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus TAS,IEA --
GO:0005886 plasma membrane TAS,IDA 11786550
GO:0005925 focal adhesion HDA 21423176
GO:0012505 endomembrane system IEA --
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with SLC9A3R2: view

Pathways & Interactions for SLC9A3R2 Gene

PathCards logo

SuperPathways for SLC9A3R2 Gene

genes like me logo Genes that share pathways with SLC9A3R2: view

Pathways by source for SLC9A3R2 Gene

2 BioSystems pathways for SLC9A3R2 Gene
1 PharmGKB pathway for SLC9A3R2 Gene
1 KEGG pathway for SLC9A3R2 Gene
3 GeneGo (Thomson Reuters) pathways for SLC9A3R2 Gene
  • Regulation of CFTR activity (norm and CF)
  • wtCFTR and delta508-CFTR traffic / Generic schema (norm and CF)
  • wtCFTR and deltaF508 traffic / Membrane expression (norm and CF)
2 Cell Signaling Technology pathways for SLC9A3R2 Gene

Gene Ontology (GO) - Biological Process for SLC9A3R2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0065003 protein-containing complex assembly TAS 9748260
genes like me logo Genes that share ontologies with SLC9A3R2: view

No data available for SIGNOR curated interactions for SLC9A3R2 Gene

Drugs & Compounds for SLC9A3R2 Gene

(7) Drugs for SLC9A3R2 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
cyclic amp Experimental Pharma 0

(4) Additional Compounds for SLC9A3R2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with SLC9A3R2: view

Transcripts for SLC9A3R2 Gene

mRNA/cDNA for SLC9A3R2 Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SLC9A3R2

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for SLC9A3R2 Gene

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

Relevant External Links for SLC9A3R2 Gene

GeneLoc Exon Structure for
SLC9A3R2

Expression for SLC9A3R2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SLC9A3R2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for SLC9A3R2 Gene

This gene is overexpressed in Breast (51.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for SLC9A3R2 Gene



Protein tissue co-expression partners for SLC9A3R2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SLC9A3R2

SOURCE GeneReport for Unigene cluster for SLC9A3R2 Gene:

Hs.440896

mRNA Expression by UniProt/SwissProt for SLC9A3R2 Gene:

Q15599-NHRF2_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for SLC9A3R2 Gene

  • Kidney(4.7)
  • Liver(4.7)
  • Lung(4.6)
  • Nervous system(4.6)
  • Intestine(3.2)
  • Heart(3.1)
  • Muscle(2.8)
  • Spleen(2.6)
  • Stomach(2.4)
  • Pancreas(2.1)
  • Thyroid gland(2)
genes like me logo Genes that share expression patterns with SLC9A3R2: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for SLC9A3R2 Gene

Orthologs for SLC9A3R2 Gene

This gene was present in the common ancestor of animals.

Orthologs for SLC9A3R2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SLC9A3R2 31
  • 98 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia SLC9A3R2 30 31
  • 89.42 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Slc9a3r2 30 17 31
  • 87.64 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Slc9a3r2 30
  • 86.84 (n)
Cow
(Bos Taurus)
Mammalia SLC9A3R2 31
  • 83 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia SLC9A3R2 31
  • 73 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SLC9A3R2 31
  • 56 (a)
OneToOne
Chicken
(Gallus gallus)
Aves SLC9A3R2 30 31
  • 72.06 (n)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia slc9a3r2 30
  • 66.27 (n)
African clawed frog
(Xenopus laevis)
Amphibia MGC68451 30
Zebrafish
(Danio rerio)
Actinopterygii SLC9A3R2 (2 of 3) 31
  • 62 (a)
OneToMany
LOC100535100 30
  • 61.99 (n)
CU571260.1 31
  • 59 (a)
OneToMany
SLC9A3R2 (1 of 3) 31
  • 50 (a)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta Sip1 31
  • 30 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea mpz-2 30
  • 43.27 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.8280 31
  • 44 (a)
OneToMany
Species where no ortholog for SLC9A3R2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • Lizard (Anolis carolinensis)
  • 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)

Evolution for SLC9A3R2 Gene

ENSEMBL:
Gene Tree for SLC9A3R2 (if available)
TreeFam:
Gene Tree for SLC9A3R2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SLC9A3R2: view image

Paralogs for SLC9A3R2 Gene

Paralogs for SLC9A3R2 Gene

(5) SIMAP similar genes for SLC9A3R2 Gene using alignment to 6 proteins:

  • NHRF2_HUMAN
  • H3BMF5_HUMAN
  • H3BN50_HUMAN
  • H3BQS0_HUMAN
  • H3BUQ9_HUMAN
  • Q6NTG0_HUMAN
genes like me logo Genes that share paralogs with SLC9A3R2: view

Variants for SLC9A3R2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SLC9A3R2 Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
781180 Benign: not provided 2,027,089(+) G/C MISSENSE_VARIANT
781320 Benign: not provided 2,036,797(+) G/A MISSENSE_VARIANT
rs387907539 Uncertain Significance: not provided 2,029,620(+) G/A SYNONYMOUS_VARIANT
rs387907540 Uncertain Significance: not provided 2,036,395(+) G/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for SLC9A3R2 Gene

Structural Variations from Database of Genomic Variants (DGV) for SLC9A3R2 Gene

Variant ID Type Subtype PubMed ID
dgv336n27 CNV loss 19166990
dgv4858n54 CNV loss 21841781
dgv4859n54 CNV loss 21841781
dgv779e212 CNV loss 25503493
esv2422427 CNV duplication 17116639
esv2750375 CNV deletion 23290073
nsv1070734 CNV deletion 25765185
nsv1160329 CNV deletion 26073780
nsv457348 CNV loss 19166990
nsv471072 CNV loss 18288195
nsv521569 CNV loss 19592680
nsv522978 CNV loss 19592680
nsv523037 CNV loss 19592680
nsv571189 CNV loss 21841781
nsv952901 CNV deletion 24416366

Variation tolerance for SLC9A3R2 Gene

Gene Damage Index Score: 4.10; 61.08% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SLC9A3R2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SLC9A3R2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SLC9A3R2 Gene

Disorders for SLC9A3R2 Gene

MalaCards: The human disease database

(6) MalaCards diseases for SLC9A3R2 Gene - From: DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards
genes like me logo Genes that share disorders with SLC9A3R2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SLC9A3R2 Gene

Publications for SLC9A3R2 Gene

  1. A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins. (PMID: 9671706) Hall RA … Lefkowitz RJ (Proceedings of the National Academy of Sciences of the United States of America 1998) 2 3 4 23
  2. NHERF2 specifically interacts with LPA2 receptor and defines the specificity and efficiency of receptor-mediated phospholipase C-beta3 activation. (PMID: 15143197) Oh YS … Suh PG (Molecular and cellular biology 2004) 3 4 23
  3. Molecular requirements for the regulation of the renal outer medullary K(+) channel ROMK1 by the serum- and glucocorticoid-inducible kinase SGK1. (PMID: 14623317) Palmada M … Lang F (Biochemical and biophysical research communications 2003) 3 4 23
  4. Isoforms of SLC26A6 mediate anion transport and have functional PDZ interaction domains. (PMID: 12444019) Lohi H … Kere J (American journal of physiology. Cell physiology 2003) 3 4 23
  5. cAMP-induced phosphorylation and inhibition of Na(+)/H(+) exchanger 3 (NHE3) are dependent on the presence but not the phosphorylation of NHE regulatory factor. (PMID: 10455146) Zizak M … Weinman EJ (The Journal of biological chemistry 1999) 3 4 23

Products for SLC9A3R2 Gene

Sources for SLC9A3R2 Gene