NHERF1 NHERF family PDZ scaffold protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NHERF1provided by HGNC
Official Full Name: NHERF family PDZ scaffold protein 1provided by HGNC
Primary source: HGNC:HGNC:11075
See related: Ensembl:ENSG00000109062 MIM:604990; AllianceGenome:HGNC:11075
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EBP50; NHERF; NHE-RF; NHERF-1; NPHLOP2; SLC9A3R1
Summary: This gene encodes a sodium/hydrogen exchanger regulatory cofactor. The protein interacts with and regulates various proteins including the cystic fibrosis transmembrane conductance regulator and G-protein coupled receptors such as the beta2-adrenergic receptor and the parathyroid hormone 1 receptor. The protein also interacts with proteins that function as linkers between integral membrane and cytoskeletal proteins. The protein localizes to actin-rich structures including membrane ruffles, microvilli, and filopodia. Mutations in this gene result in hypophosphatemic nephrolithiasis/osteoporosis type 2, and loss of heterozygosity of this gene is implicated in breast cancer.[provided by RefSeq, Sep 2009]
Expression: Broad expression in small intestine (RPKM 101.8), duodenum (RPKM 91.7) and 23 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q25.1

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (74748628..74769353)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (75640506..75661228)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (72744767..72765492)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

High frequency of heterozygous rare variants of the SLC34A1 and SLC9A3R1 genes in patients with atypical femur fracture.
Title: High frequency of heterozygous rare variants of the SLC34A1 and SLC9A3R1 genes in patients with atypical femur fracture.
RGS14 regulates PTH- and FGF23-sensitive NPT2A-mediated renal phosphate uptake via binding to the NHERF1 scaffolding protein.
Title: RGS14 regulates PTH- and FGF23-sensitive NPT2A-mediated renal phosphate uptake via binding to the NHERF1 scaffolding protein.
Cotranslational interaction of human EBP50 and ezrin overcomes masked binding site during complex assembly.
Title: Cotranslational interaction of human EBP50 and ezrin overcomes masked binding site during complex assembly.
Nuclear expression of NHERF1/EBP50 in Clear Cell Renal Cell Carcinoma.
Title: Nuclear expression of NHERF1/EBP50 in Clear Cell Renal Cell Carcinoma.
Cytoplasmic EBP50 and elevated PARP1 are unfavorable prognostic factors in ovarian clear cell carcinoma.
Title: Cytoplasmic EBP50 and elevated PARP1 are unfavorable prognostic factors in ovarian clear cell carcinoma.
Na(+)/H(+) Exchanger Regulatory Factor 1 Mediates the Pathogenesis of Airway Inflammation in a Murine Model of House Dust Mite-Induced Asthma.
Title: Na(+)/H(+) Exchanger Regulatory Factor 1 Mediates the Pathogenesis of Airway Inflammation in a Murine Model of House Dust Mite-Induced Asthma.
Multisite NHERF1 phosphorylation controls GRK6A regulation of hormone-sensitive phosphate transport.
Title: Multisite NHERF1 phosphorylation controls GRK6A regulation of hormone-sensitive phosphate transport.
Noncanonical Sequences Involving NHERF1 Interaction with NPT2A Govern Hormone-Regulated Phosphate Transport: Binding Outside the Box.
Title: Noncanonical Sequences Involving NHERF1 Interaction with NPT2A Govern Hormone-Regulated Phosphate Transport: Binding Outside the Box.
Sodium Hydrogen Exchanger Regulatory Factor-1 (NHERF1) Regulates Fetal Membrane Inflammation.
Title: Sodium Hydrogen Exchanger Regulatory Factor-1 (NHERF1) Regulates Fetal Membrane Inflammation.
In vivo crystals reveal critical features of the interaction between cystic fibrosis transmembrane conductance regulator (CFTR) and the PDZ2 domain of Na(+)/H(+) exchange cofactor NHERF1.
Title: In vivo crystals reveal critical features of the interaction between cystic fibrosis transmembrane conductance regulator (CFTR) and the PDZ2 domain of Na(+)/H(+) exchange cofactor NHERF1.

Submit: New GeneRIF Correction See all GeneRIFs (163)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hypophosphatemic nephrolithiasis/osteoporosis 2 MedGen: C2676782 OMIM: 612287 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Novel loci, including those related to Crohn disease, psoriasis, and inflammation, identified in a genome-wide association study of fibrinogen in 17 686 women: the Women's Genome Health Study. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	NHERF1 is required for HIV-1 gp120-induced actin rearrangement	PubMed
	env	Binding of HIV-1 gp120 to CCR5 causes NHERF1-mediated activation of RhoA	PubMed
	env	HIV-1 gp120-stimulated cells overexpressing NHERF1 upregulates FAK phosphorylation	PubMed
	env	NHERF1 increases ERK1/2 phosphorylation levels following HIV-1 gp120 stimulation in cells	PubMed
	env	Stimulation of cells with HIV-1 gp120 induces the interaction of endogenous CCR5 with NHERF1, which leads to enhanced CCR5 internalization	PubMed
reverse transcriptase	gag-pol	HIV-1 RT is identified to have a physical interaction with solute carrier family 9, member 3 regulator 1 (SLC9A3R1; NHERF) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH92683 (e-PCR)
- UniSTS:88578

D10S275 (e-PCR)
- UniSTS:147992

D8S2279 (e-PCR)
- UniSTS:473907

G19962 (e-PCR)
- UniSTS:15965

A002D35 (e-PCR)
- UniSTS:15966

D10S16 (e-PCR)
- UniSTS:155756

G35510 (e-PCR)
- UniSTS:44150

RH98250 (e-PCR)
- UniSTS:90231

RH36905 (e-PCR)
- UniSTS:87932

HUM000S150 (e-PCR)
- UniSTS:40361

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables PDZ domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables beta-2 adrenergic receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables beta-catenin binding	IPI Inferred from Physical Interaction more info	PubMed
enables channel activator activity	IDA Inferred from Direct Assay more info	PubMed
enables chloride channel regulator activity	IDA Inferred from Direct Assay more info	PubMed
enables dopamine receptor binding	IEA Inferred from Electronic Annotation more info
contributes_to gamma-aminobutyric acid transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
enables growth factor receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables myosin II binding	IEA Inferred from Electronic Annotation more info
enables phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info
enables protein-membrane adaptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables signaling receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmembrane transporter binding	IEA Inferred from Electronic Annotation more info
enables type 2 metabotropic glutamate receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables type 3 metabotropic glutamate receptor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in actin cytoskeleton organization	IEA Inferred from Electronic Annotation more info
involved_in adenylate cyclase-activating dopamine receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in auditory receptor cell stereocilium organization	IEA Inferred from Electronic Annotation more info
involved_in bile acid secretion	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within cerebrospinal fluid circulation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cilium organization	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in establishment of Golgi localization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in establishment of epithelial cell apical/basal polarity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in fibroblast migration	IEA Inferred from Electronic Annotation more info
involved_in gamma-aminobutyric acid import	ISS Inferred from Sequence or Structural Similarity more info
involved_in gland morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glutathione transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in import across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in intracellular phosphate ion homeostasis	IEA Inferred from Electronic Annotation more info
involved_in maintenance of epithelial cell apical/basal polarity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in maintenance of epithelial cell apical/basal polarity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in microvillus assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within morphogenesis of an epithelium	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of canonical Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of fibroblast migration	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of platelet-derived growth factor receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of sodium ion transport	IEA Inferred from Electronic Annotation more info
involved_in nuclear migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phospholipase C-activating dopamine receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in plasma membrane organization	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of intrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in protein localization to plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein-containing complex assembly	TAS Traceable Author Statement more info	PubMed
involved_in regulation of cell shape	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cell size	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein kinase activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of renal phosphate excretion	IEA Inferred from Electronic Annotation more info
involved_in renal absorption	ISS Inferred from Sequence or Structural Similarity more info
involved_in renal phosphate ion absorption	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in renal sodium ion transport	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of sound	IEA Inferred from Electronic Annotation more info
involved_in transport across blood-brain barrier	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in actin cytoskeleton	TAS Traceable Author Statement more info	PubMed
is_active_in apical plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in brush border membrane	IEA Inferred from Electronic Annotation more info
located_in cell periphery	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in endomembrane system	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in filopodium	IEA Inferred from Electronic Annotation more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in microvillus	IDA Inferred from Direct Assay more info	PubMed
located_in microvillus membrane	ISS Inferred from Sequence or Structural Similarity more info
NOT located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
part_of plasma membrane protein complex	ISS Inferred from Sequence or Structural Similarity more info
located_in ruffle	IEA Inferred from Electronic Annotation more info
located_in sperm midpiece	ISS Inferred from Sequence or Structural Similarity more info
located_in stereocilium tip	IEA Inferred from Electronic Annotation more info
located_in vesicle	HDA more info	PubMed

General protein information

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Preferred Names: Na(+)/H(+) exchange regulatory cofactor NHE-RF1

Names: Na(+)/H(+) exchange regulatory cofactor 1; Na+/H+ exchange regulatory co-factor; SLC9A3 regulator 1; ezrin-radixin-moesin binding phosphoprotein-50; regulatory cofactor of Na(+)/H(+) exchanger; solute carrier family 9, subfamily A (NHE3, cation proton antiporter 3), member 3 regulator 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013022.1 RefSeqGene

Range

5005..25730

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004252.5 → NP_004243.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF1

See identical proteins and their annotated locations for NP_004243.1

Status: REVIEWED

Source sequence(s)

BC053350, CX761192

Consensus CDS

CCDS11705.1

UniProtKB/Swiss-Prot

B3KY21, O14745, O43552, Q86WQ5

UniProtKB/TrEMBL

B2R6A3

Related

ENSP00000262613.5, ENST00000262613.10

Conserved Domains (2) summary

cd00992
Location:12 → 91

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

pfam09007
Location:235 → 358

EBP50_C; EBP50, C-terminal