NHERF2 NHERF family PDZ scaffold protein 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NHERF2provided by HGNC
Official Full Name: NHERF family PDZ scaffold protein 2provided by HGNC
Primary source: HGNC:HGNC:11076
See related: Ensembl:ENSG00000065054 MIM:606553; AllianceGenome:HGNC:11076
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: SIP1; OCTS2; SIP-1; TKA-1; E3KARP; NHE3RF2; NHERF-2; SLC9A3R2
Summary: 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]
Expression: Broad expression in fat (RPKM 26.8), lung (RPKM 19.5) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16p13.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (2026902..2039026)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (2046859..2058835)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (2076903..2089027)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PDZ domain-containing protein NHERF-2 is a novel target of HPV-16 and HPV-18 E proteins.
Title: PDZ Domain-Containing Protein NHERF-2 Is a Novel Target of Human Papillomavirus 16 (HPV-16) and HPV-18.
Studies support a role for NHERF-1 and NHERF-2 (Na+/H+ exchanger regulatory factors 1 and 2) in regulating the distribution of Group II metabotropic glutamate receptor (mGluRs) in the murine brain, while conversely the effects of the mGluR2/3 PDZ-binding motifs on receptor signaling are likely mediated by interactions with other PDZ scaffold proteins beyond the NHERF proteins.
Title: Group II metabotropic glutamate receptor interactions with NHERF scaffold proteins: Implications for receptor localization in brain.
Moreover, the S303D mutation enhances the in vivo dynamics of the E3KARP tail alone, whereas in vitro the interaction of E3KARP with active ezrin is unaffected by S303D
Title: The function and dynamics of the apical scaffolding protein E3KARP are regulated by cell-cycle phosphorylation.
Lysophosphatidic acid stimulation of NHE3 exocytosis in polarized epithelial cells occurs with release from NHERF2 via ERK-PLC-PKCdelta signaling.
Title: Lysophosphatidic acid stimulation of NHE3 exocytosis in polarized epithelial cells occurs with release from NHERF2 via ERK-PLC-PKCδ signaling.
Data indicate that the tails promote different microvillar localizations for EBP50 and E3KARP, which localized along the full length and to the base of microvilli, respectively.
Title: The tails of apical scaffolding proteins EBP50 and E3KARP regulate their localization and dynamics.
Crystal structure of NHERF2 PDZ1 domain complex with C-terminal LPA2 sequence. The PDZ1-LPA2 binding specificity is achieved by hydrogen bonds and hydrophobic contacts with the last four LPA2 residues contributing to specific interactions.
Title: Structural insights into PDZ-mediated interaction of NHERF2 and LPA(2), a cellular event implicated in CFTR channel regulation.
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.
functional regulation of C3aR by NHERFs in human mast cells
Title: Roles for NHERF1 and NHERF2 on the regulation of C3a receptor signaling in human mast cells.
AnxA2 and NHERF2 form a scaffold complex that links adjacent Tir molecules at the plasma membrane forming a lattice that could be involved in retention and dissemination of other effectors at the bacterial attachment site.
Title: Recruitment and membrane interactions of host cell proteins during attachment of enteropathogenic and enterohaemorrhagic Escherichia coli.
NHERF-2 is a negative regulator of endothelial proliferation and may have important roles in endothelial homeostasis and vascular modeling.
Title: NHERF-2 maintains endothelial homeostasis.

Submit: New GeneRIF Correction See all GeneRIFs (31)

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

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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Replication interactions

Interaction	Pubs
Knockdown of solute carrier family 9, subfamily A (NHE3, cation proton antiporter 3), member 3 regulator 2 (SLC9A3R2) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-Z50150 (e-PCR)
- UniSTS:78140

RH48490 (e-PCR)
- UniSTS:54443

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables beta-catenin binding	IPI Inferred from Physical Interaction more info	PubMed
enables cadherin binding	HDA more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphatase binding	IPI Inferred from Physical Interaction more info	PubMed
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	IPI Inferred from Physical Interaction more info	PubMed
enables type 2 metabotropic glutamate receptor binding	ISS Inferred from Sequence or Structural Similarity more info
enables type 3 metabotropic glutamate receptor binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in protein localization to plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein-containing complex assembly	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
is_active_in apical plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in endomembrane system	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in focal adhesion	HDA more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	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; NHE3 regulatory factor 2; Na(+)/H(+) exchange regulatory cofactor 2; SLC9A3 regulator 2; SRY-interacting protein 1; sodium/hydrogen exchanger 3 kinase A regulatory protein; 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.

Genomic

NG_047104.1 RefSeqGene

Range

5035..17159

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001130012.3 → NP_001123484.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform a

See identical proteins and their annotated locations for NP_001123484.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).

Source sequence(s)

AC093513, BC014513

Consensus CDS

CCDS45382.1

UniProtKB/Swiss-Prot

D3DU84, D3DU85, H3BSV6, O00272, O00556, Q15599, Q3KQY7

UniProtKB/TrEMBL

Q6NTG0

Related

ENSP00000408005.2, ENST00000424542.7

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
NM_001252073.2 → NP_001239002.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (c) is shorter and has a distinct N-terminus, compared to isoform a.

Source sequence(s)

AC093513, BX377861, CB961565

Consensus CDS

CCDS58407.1

UniProtKB/TrEMBL

H3BN50

Related

ENSP00000456895.1, ENST00000566198.1

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
NM_001252075.2 → NP_001239004.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (d) is shorter and has a distinct N-terminus, compared to isoform a.

Source sequence(s)

AC093513, CB961565

UniProtKB/TrEMBL

H3BN50

Related

ENSP00000454690.1, ENST00000565855.5

Conserved Domains (2) summary

cd00992
Location:36 → 115

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:119 → 224

EBP50_C; EBP50, C-terminal
NM_001252076.2 → NP_001239005.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR, uses an alternate splice site in the 3' coding region, lacks a portion of the 5' coding region and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (e) is shorter and has a distinct N-terminus, compared to isoform a.

Source sequence(s)

AC093513, BQ687174, CB961565

UniProtKB/TrEMBL

H3BN50

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 → 215

EBP50_C; EBP50, C-terminal
NM_004785.6 → NP_004776.3 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform b

See identical proteins and their annotated locations for NP_004776.3

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (b) is shorter than isoform a.

Source sequence(s)

AC093513, U82108

Consensus CDS

CCDS45383.1

UniProtKB/TrEMBL

Q6NTG0

Related

ENSP00000402857.2, ENST00000432365.6

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 → 326

EBP50_C; EBP50, C-terminal

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

2026902..2039026

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047434923.1 → XP_047290879.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X3
XM_047434924.1 → XP_047290880.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X4

UniProtKB/TrEMBL

H3BN50, H3BQS0

Related

ENSP00000455909.1, ENST00000563587.5
XM_017023894.2 → XP_016879383.2 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X1

UniProtKB/TrEMBL

H3BN50
XM_005255702.5 → XP_005255759.2 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X2

UniProtKB/TrEMBL

H3BUQ9

Related

ENSP00000457755.1, ENST00000561844.5
XM_024450492.2 → XP_024306260.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X6

UniProtKB/TrEMBL

H3BN50

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 → 191

EBP50_C; EBP50, C-terminal
XM_006720981.2 → XP_006721044.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X5

See identical proteins and their annotated locations for XP_006721044.1

UniProtKB/TrEMBL

H3BN50

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

Alternate T2T-CHM13v2.0

Genomic

NC_060940.1 Alternate T2T-CHM13v2.0

Range

2046859..2058835

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054314430.1 → XP_054170405.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X9

UniProtKB/TrEMBL

Q6NTG0
XM_054314432.1 → XP_054170407.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X11

UniProtKB/TrEMBL

H3BN50
XM_054314431.1 → XP_054170406.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X10
XM_054314427.1 → XP_054170402.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X7

UniProtKB/TrEMBL

H3BN50
XM_054314428.1 → XP_054170403.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X8

UniProtKB/TrEMBL

H3BN50
XM_054314429.1 → XP_054170404.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X1

UniProtKB/TrEMBL

H3BN50
XM_054314433.1 → XP_054170408.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X12

UniProtKB/TrEMBL

H3BN50
XM_054314434.1 → XP_054170409.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X5

UniProtKB/TrEMBL

H3BN50
XM_054314435.1 → XP_054170410.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 isoform X6

UniProtKB/TrEMBL

H3BN50