NHERF4 NHERF family PDZ scaffold protein 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NHERF4provided by HGNC
Official Full Name: NHERF family PDZ scaffold protein 4provided by HGNC
Primary source: HGNC:HGNC:19891
See related: Ensembl:ENSG00000172367 MIM:607146; AllianceGenome:HGNC:19891
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IKEPP; PDZD3; PDZK2
Summary: Guanylyl cyclase C (GCC, or GUCY2C; MIM 601330) produces cGMP following the binding of either endogenous ligands or heat-stable enterotoxins secreted by E. coli and other enteric bacteria. Activation of GCC initiates a signaling cascade that leads to phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR; MIM 602421), followed by a net efflux of ions and water into the intestinal lumen. IKEPP is a regulatory protein that associates with GCC and regulates the amount of cGMP produced following receptor stimulation (Scott et al., 2002 [PubMed 11950846]).[supplied by OMIM, Mar 2008]
Expression: Biased expression in duodenum (RPKM 18.4), small intestine (RPKM 16.9) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q23.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (119185475..119190213)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (119205845..119210583)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (119056184..119060922)

Chromosome 11 - NC_000011.10 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 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?

The NHERF4 is a novel modulator of luminal fluidity in the intestine by adjusting SLC26A3 expression and activity through a phosphorylation-dependent mechanism.
Title: Regulation of SLC26A3 activity by NHERF4 PDZ-mediated interaction.
IKEPP was also found to be expressed in vascular endothelial cells where it co-localizes and complexes with the hIP
Title: Interaction of the human prostacyclin receptor and the NHERF4 family member intestinal and kidney enriched PDZ protein (IKEPP).
Regulation of NHE3 depends on the nature of the NHERF family member associating with NHE3 and the accompanying NHE3 complexes.
Title: Elevated intracellular calcium stimulates NHE3 activity by an IKEPP (NHERF4) dependent mechanism.
A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor.
Title: A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor.

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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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-16056 (e-PCR)
- UniSTS:53534

RH94032 (e-PCR)
- UniSTS:91629

RH48721 (e-PCR)
- UniSTS:15611

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables guanylate cyclase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
enables ion channel inhibitor activity	TAS Traceable Author Statement 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 ubiquitin-specific protease binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in monoatomic ion transport	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of cGMP-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in protein localization to plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in receptor guanylyl cyclase signaling pathway	IC Inferred by Curator more info	PubMed
involved_in response to toxic substance	TAS Traceable Author Statement more info	PubMed
involved_in water transport	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in apical junction complex	IDA Inferred from Direct Assay more info	PubMed
located_in apical part of cell	IDA Inferred from Direct Assay more info	PubMed
is_active_in apical plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in brush border	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info	PubMed
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-RF4

Names: NHERF-4; Na(+)/H(+) exchange regulatory cofactor 4; PDZ domain containing 2; PDZ domain containing 3; PDZ domain-containing protein 2; PDZ domain-containing protein 3; intestinal and kidney enriched PDZ protein; na/Pi cotransporter C-terminal-associated protein 2; naPi-Cap2; natrium-phosphate cotransporter IIa C-terminal-associated protein 2; sodium-hydrogen exchanger regulatory factor 4

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_001168468.2 → NP_001161940.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform 1

See identical proteins and their annotated locations for NP_001161940.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AB094096, AY047359, DA381610

Consensus CDS

CCDS53719.1

UniProtKB/TrEMBL

B4DPH0

Related

ENSP00000347742.5, ENST00000355547.10

Conserved Domains (1) summary

cd00992
Location:47 → 127

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) ...
NM_024791.4 → NP_079067.3 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform 2

See identical proteins and their annotated locations for NP_079067.3

Status: VALIDATED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the central coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AB094096, AP002956, BC029042, DA381610

Consensus CDS

CCDS8417.1

UniProtKB/TrEMBL

B0YJ61, B4DPH0

Related

ENSP00000327107.4, ENST00000322712.4

Conserved Domains (1) summary

cd00992
Location:47 → 127

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) ...

RNA

NR_033122.2 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (3) uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AB094096, AK298333, AP002956

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_000011.10 Reference GRCh38.p14 Primary Assembly

Range

119185475..119190213

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011543002.3 → XP_011541304.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X1

See identical proteins and their annotated locations for XP_011541304.1

UniProtKB/Swiss-Prot

Q86UT5, Q8N6R4, Q8NAW7, Q8NEX7, Q9H5Z3

UniProtKB/TrEMBL

B4DPH0

Related

ENSP00000431164.1, ENST00000531114.5

Conserved Domains (2) summary

smart00228
Location:326 → 411

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

cd00992
Location:113 → 193

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) ...
XM_011543001.3 → XP_011541303.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X1

See identical proteins and their annotated locations for XP_011541303.1

UniProtKB/Swiss-Prot

Q86UT5, Q8N6R4, Q8NAW7, Q8NEX7, Q9H5Z3

UniProtKB/TrEMBL

B4DPH0

Conserved Domains (2) summary

smart00228
Location:326 → 411

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

cd00992
Location:113 → 193

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) ...
XM_011543005.3 → XP_011541307.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X3

UniProtKB/TrEMBL

B4DPH0

Related

ENST00000527028.5

Conserved Domains (1) summary

cd00992
Location:48 → 128

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) ...
XM_017018334.2 → XP_016873823.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X2

UniProtKB/TrEMBL

B4DPH0

Conserved Domains (2) summary

smart00228
Location:312 → 397

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

cd00992
Location:113 → 193

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) ...
XM_047427615.1 → XP_047283571.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X4

UniProtKB/TrEMBL

E9PPZ1

Related

ENSP00000434559.1, ENST00000525131.5
XM_017018335.2 → XP_016873824.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X5

Conserved Domains (1) summary

cd00992
Location:113 → 193

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) ...
XM_017018336.2 → XP_016873825.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X6

Conserved Domains (1) summary

cd00992
Location:113 → 193

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) ...
XM_017018337.2 → XP_016873826.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X7

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

119205845..119210583

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054369993.1 → XP_054225968.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X1

UniProtKB/Swiss-Prot

Q86UT5, Q8N6R4, Q8NAW7, Q8NEX7, Q9H5Z3
XM_054369995.1 → XP_054225970.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X3
XM_054369994.1 → XP_054225969.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X2
XM_054369996.1 → XP_054225971.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X4

UniProtKB/TrEMBL

E9PPZ1
XM_054369997.1 → XP_054225972.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X5
XM_054369998.1 → XP_054225973.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X6
XM_054369999.1 → XP_054225974.1 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X7