Nherf2 NHERF family PDZ scaffold protein 2 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Nherf2provided by RGD
Official Full Name: NHERF family PDZ scaffold protein 2provided by RGD
Primary source: RGD:620380
See related: Ensembl:ENSRNOG00000002997 AllianceGenome:RGD:620380
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: E3karp; Slc9a3r2
Summary: Enables low-density lipoprotein particle receptor binding activity; molecular adaptor activity; and protein N-terminus binding activity. Involved in inner ear development and positive regulation of ion transmembrane transport. Located in apical plasma membrane and nucleus. Part of protein-containing complex. Biomarker of hypertension. Orthologous to human SLC9A3R2 (SLC9A3 regulator 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Lung (RPKM 311.8), Heart (RPKM 203.5) and 8 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 10q12

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	10	NC_086028.1 (14167005..14177519, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	10	NC_051345.1 (13662461..13672975, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	10	NC_005109.4 (14003330..14015066, complement)

Chromosome 10 - NC_086028.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The results suggest that NHERF1 and NHERF2 down-regulated SR-B1 at least in part via the ubiquitin/proteasome pathway.
Title: NHERF1 and NHERF2 regulation of SR-B1 stability via ubiquitination and proteasome degradation.
NHERF2 domain was functionally significant in NHE3 regulation, being necessary for stimulation by lysophosphatidic acid of activity and increased mobility of NHE3
Title: NHERF2 protein mobility rate is determined by a unique C-terminal domain that is also necessary for its regulation of NHE3 protein in OK cells.
data establish NHERF1 and NHERF2 as SR-BI protein binding partners that play a negative role in the regulation of SR-BI expression, selective CE transport, and steroidogenesis.
Title: Regulation of expression and function of scavenger receptor class B, type I (SR-BI) by Na+/H+ exchanger regulatory factors (NHERFs).
The cochlear localization of NHERF scaffolds suggests that they play important roles in the developmental regulation of ion transport, homeostasis, and auditory neurotransmission.
Title: Postnatal developmental expression of the PDZ scaffolds Na+ -H+ exchanger regulatory factors 1 and 2 in the rat cochlea.
NHERF2 selectively restricts downstream coupling of mGluR5 and P2Y1Rs in neurons to G(q)-mediated responses. Differential distribution of NHERF2 in neurons may therefore determine coupling of mGluR5 and P2Y1 receptors to calcium channels.
Title: The scaffold protein NHERF2 determines the coupling of P2Y1 nucleotide and mGluR5 glutamate receptor to different ion channels in neurons.
These findings implicate the GLAST-NHERF1 complex in the regulation of glutamate homeostasis in astrocytes.
Title: Na+-H+ exchanger regulatory factor 1 is a PDZ scaffold for the astroglial glutamate transporter GLAST.
NHERF2 stimulates PDGF-induced proliferation by increasing PI-3-kinase/Akt, MEKindependent ERK, and Src family kinase-mediated signaling pathways
Title: NHERF2 increases platelet-derived growth factor-induced proliferation through PI-3-kinase/Akt-, ERK-, and Src family kinase-dependent pathway.
decreased expression of NHERF1 may be related to the enhanced NHE activity in SHR and that these changes are likely to be genetically determined, whereas the increased NHERF2 expression may be induced as a compensatory mechanism
Title: Expression of the Na+/H+ exchanger regulatory protein family in genetically hypertensive rats.
Since ASIC3 sustained current in nociceptor excitability, it is likely that NHERF-1 participates in channel functions associated with nociception and mechanosensation.
Title: Regulation of sensory neuron-specific acid-sensing ion channel 3 by the adaptor protein Na+/H+ exchanger regulatory factor-1.

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by RGD

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

Process	Evidence Code	Pubs
involved_in inner ear development	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
acts_upstream_of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of monoatomic ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
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	ISO Inferred from Sequence Orthology more info

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	ISO Inferred from Sequence Orthology more info
located_in endomembrane system	IEA Inferred from Electronic Annotation more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
located_in stereocilium	ISO Inferred from Sequence Orthology more info
located_in stereocilium bundle	ISO Inferred from Sequence Orthology more info

General protein information

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

Names: NHE3 kinase A regulatory protein E3KARP; NHERF-2; SIP-1; SLC9A3 regulator 2; SRY-interacting protein 1; TKA-1; sodium-hydrogen exchanger regulatory factor 2; sodium/hydrogen exchanger; solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 2; solute carrier family 9, subfamily A (NHE3, cation proton antiporter 3), 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_053811.3 → NP_446263.2 Na(+)/H(+) exchange regulatory cofactor NHE-RF2

See identical proteins and their annotated locations for NP_446263.2

Status: VALIDATED

Source sequence(s)

AF294257, CK840521, JAXUCZ010000010

UniProtKB/Swiss-Prot

Q91Y70, Q920G2

UniProtKB/TrEMBL

A6HCU6, G3V6D9

Related

ENSRNOP00000004172.2, ENSRNOT00000004172.5

Conserved Domains (2) summary

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

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086028.1 Reference GRCr8

Range

14167005..14177519 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_039085043.2 → XP_038940971.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X2

UniProtKB/TrEMBL

A0A8I6A0E3

Conserved Domains (2) summary

cd00992
Location:18 → 97

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:101 → 206

EBP50_C; EBP50, C-terminal
XM_006245893.5 → XP_006245955.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X1

See identical proteins and their annotated locations for XP_006245955.1

UniProtKB/TrEMBL

A0A8I6A0E3, A6HCU7

Related

ENSRNOP00000085544.1

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
XM_039085044.2 → XP_038940972.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X3

UniProtKB/TrEMBL

A0A8I6A0E3

Conserved Domains (2) summary

cd00992
Location:14 → 93

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:97 → 202

EBP50_C; EBP50, C-terminal