Nherf2 NHERF family PDZ scaffold protein 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Nherf2provided by MGI
Official Full Name: NHERF family PDZ scaffold protein 2provided by MGI
Primary source: MGI:MGI:1890662
See related: Ensembl:ENSMUSG00000002504 AllianceGenome:MGI:1890662
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Sip1; Octs2; Sip-1; Tka-1; E3karp; Sryip1; NHERF-2; Slc9a3r2; 0610011L07Rik; 1200011K07Rik; 2010007A20Rik
Summary: Enables phosphatase binding activity. Acts upstream of or within negative regulation of phosphatidylinositol 3-kinase signaling and sensory perception of sound. Located in several cellular components, including apical plasma membrane; nucleus; and stereocilium. Is expressed in cochlea epithelium and organ of Corti. Orthologous to human SLC9A3R2 (SLC9A3 regulator 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in lung adult (RPKM 219.2), ovary adult (RPKM 58.5) and 18 other tissues See more
Orthologs: human all
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Genomic context

Location:: 17 A3.3; 17 12.43 cM

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	17	NC_000083.7 (24858255..24869279, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	17	NC_000083.6 (24639281..24650305, complement)

Chromosome 17 - NC_000083.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

NHERF2 and NHERF3 have overlapping roles in NHE3 stimulation by LPA and inhibition by elevated Ca(2+) and cGMP.
Title: Both NHERF3 and NHERF2 are necessary for multiple aspects of acute regulation of NHE3 by elevated Ca(2+), cGMP, and lysophosphatidic acid.
LRBA deficiency is associated with a reduced abundance of radixin and Nherf2, two adaptor proteins, which are important for the mechanical stability of the basal taper region of stereocilia.
Title: The BEACH protein LRBA is required for hair bundle maintenance in cochlear hair cells and for hearing.
Knockdown of NHERF2 decreased colon cancer progression. NHERF2 deletion attenuated Stat3 activation and CD24 expression in colon cancer cells.
Title: Deletion of Na+/H+ exchanger regulatory factor 2 represses colon cancer progress by suppression of Stat3 and CD24.
NHERF2 is differentially distributed to lipid rafts in brush border membrane fractions of NHE3.
Title: Differential association of the Na+/H+ Exchanger Regulatory Factor (NHERF) family of adaptor proteins with the raft- and the non-raft brush border membrane fractions of NHE3.
involvement of NHERF2 in multiple apical regulatory processes and interactions with luminal contents
Title: Alterations in the proteome of the NHERF2 knockout mouse jejunal brush border membrane vesicles.
NHERF2 is necessary for multiple aspects of acute regulation of NHE3 in intact mouse small intestine
Title: NHERF2 is necessary for basal activity, second messenger inhibition, and LPA stimulation of NHE3 in mouse distal ileum.
It was concluded that NHERF2 plays important roles in tethering NHE3 to a position near the terminal web and in second messenger inhibition of NHE3 in a signal- and segment-specific fashion.
Title: Loss of PDZ-adaptor protein NHERF2 affects membrane localization and cGMP- and [Ca2+]- but not cAMP-dependent regulation of Na+/H+ exchanger 3 in murine intestine.
Lysophosphatidic acid (LPA) is a potent stimulant of NHE3 and fluid absorption in the intestine, signaling through LPA(5). Regulation by LPA(5) depends on its interaction with NHERF2.
Title: Lysophosphatidic acid stimulates the intestinal brush border Na(+)/H(+) exchanger 3 and fluid absorption via LPA(5) and NHERF2.
CFTR-dependent duodenal bicarbonate-ion secretion in mouse models of NHERF-2 loss of function.
Title: Differential roles of NHERF1, NHERF2, and PDZK1 in regulating CFTR-mediated intestinal anion secretion in mice.
Knockout mice for 3 members of the sodium-hydrogen regulatory factor (NHERF) family of PDZ adaptor proteins, NHERF1 (EBP50), NHERF2 (E3KARP) and NHERF3 (PDZK1), have helped to show that NHERF1 is essential for both normal and mutant CFTR function [review]
Title: Knockout mouse models for intestinal electrolyte transporters and regulatory PDZ adaptors: new insights into cystic fibrosis, secretory diarrhoea and fructose-induced hypertension.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Gene trapped (2) 1 citation
Targeted (1)
Endonuclease-mediated (1)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables beta-catenin binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables low-density lipoprotein particle receptor binding	ISO Inferred from Sequence Orthology more info
enables molecular adaptor activity	ISO Inferred from Sequence Orthology more info
enables phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphatase binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
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	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of monoatomic ion transmembrane transport	ISO Inferred from Sequence Orthology more info
involved_in protein localization to plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within sensory perception of sound	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
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 apical plasma membrane	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
located_in stereocilium	IDA Inferred from Direct Assay more info	PubMed
located_in stereocilium bundle	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: Na(+)/H(+) exchange regulatory cofactor NHE-RF2

Names: NHE3 kinase A regulatory protein E3KARP; SRY-interacting protein 1; sodium-hydrogen exchanger regulatory factor 2; solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 2; tyrosine kinase activator protein 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.

mRNA and Protein(s)

NM_001357796.1 → NP_001344725.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform C

Status: VALIDATED

Source sequence(s)

AK075813, BC070458

Consensus CDS

CCDS89012.1

UniProtKB/Swiss-Prot

Q3TDR3, Q6P074, Q8BGL9, Q8BW05, Q9DCR6, Q9JHL1

UniProtKB/TrEMBL

Q6NS54

Related

ENSMUSP00000157103.2, ENSMUST00000234557.2

Conserved Domains (3) summary

smart00228
Location:148 → 230

PDZ; Domain present in PSD-95, Dlg, and ZO-1/2

cd00992
Location:9 → 88

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:232 → 316

EBP50_C; EBP50, C-terminal
NM_023055.2 → NP_075542.2 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform A

See identical proteins and their annotated locations for NP_075542.2

Status: VALIDATED

Description

Transcript Variant: This variant (A) encodes the longer isoform (A).

Source sequence(s)

AK084801, CJ194744

Consensus CDS

CCDS28488.1

UniProtKB/Swiss-Prot

Q3TDR3, Q6P074, Q8BGL9, Q8BW05, Q9DCR6, Q9JHL1

UniProtKB/TrEMBL

A0A0R4IZX2

Related

ENSMUSP00000002572.5, ENSMUST00000002572.6

Conserved Domains (3) summary

smart00228
Location:148 → 230

PDZ; Domain present in PSD-95, Dlg, and ZO-1/2

cd00992
Location:9 → 88

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:232 → 337

EBP50_C; EBP50, C-terminal
NM_023449.3 → NP_075938.2 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform B

See identical proteins and their annotated locations for NP_075938.2

Status: VALIDATED

Description

Transcript Variant: This variant (B) differs in the 5' UTR and 5' coding region, compared to variant A. The resulting isoform (B) has a shorter and distinct N-terminus, compared to isoform A.

Source sequence(s)

AK002557, AK039491, CJ194744

Consensus CDS

CCDS28489.1

UniProtKB/TrEMBL

A0A0R4J006, A0A3Q4EBU8

Related

ENSMUSP00000019684.6, ENSMUST00000019684.13

Conserved Domains (2) summary

cd00992
Location:38 → 117

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:121 → 226

EBP50_C; EBP50, C-terminal

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000083.7 Reference GRCm39 C57BL/6J

Range

24858255..24869279 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030249980.2 → XP_030105840.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X1

UniProtKB/TrEMBL

A0A3Q4EHM9

Related

ENSMUSP00000157065.2, ENSMUST00000234505.2

Conserved Domains (2) summary

cd00992
Location:38 → 117

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:121 → 205

EBP50_C; EBP50, C-terminal