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

Gene ID: 79849, updated on 2-Nov-2024

Summary

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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
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Genomic context

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See NHERF4 in Genome Data Viewer
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_000011.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3971 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:119027357-119027857 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:119029281-119029780 Neighboring gene ATP binding cassette subfamily G member 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:119039524-119040229 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:119040230-119040934 Neighboring gene NLR family member X1 Neighboring gene Sharpr-MPRA regulatory region 11099 Neighboring gene small nucleolar RNA, C/D box 150 Neighboring gene dynein regulatory complex subunit 12 homolog Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3973 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3974 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3975 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3976 Neighboring gene fragile site, folic acid type, rare, fra(11)(q23.3) Neighboring gene Cbl proto-oncogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5627 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5628 Neighboring gene RNA, U6 small nuclear 262, pseudogene

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Beyond the brush border: NHERF4 blazes new NHERF turf. Thelin WR, et al. J Physiol, 2005 Aug 15. PMID 15994182, Free PMC Article
  2. Nurturing you network: a first step to becoming a successful entrepreneur/intrapreneur. Hacker B. Pa Nurse, 1992 Mar. PMID 1553237
  3. Interaction of the human prostacyclin receptor and the NHERF4 family member intestinal and kidney enriched PDZ protein (IKEPP). Reid HM, et al. Biochim Biophys Acta, 2012 Oct. PMID 22884631
  4. A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor. Scott RO, et al. J Biol Chem, 2002 Jun 21. PMID 11950846
  5. Regulation of SLC26A3 activity by NHERF4 PDZ-mediated interaction. Lee JH, et al. Cell Signal, 2012 Sep. PMID 22627094

See all (19) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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).
  3. 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.
  4. 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.
Submit: New GeneRIF Correction

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)

Genotypes

Pathways from PubChem

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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

Homology

Clone Names

  • FLJ22756

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)

  1. 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) ...

  2. 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

  1. 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

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    119185475..119190213
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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) ...

  2. 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) ...

  3. 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) ...

  4. 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) ...

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

    UniProtKB/TrEMBL
    E9PPZ1
    Related
    ENSP00000434559.1, ENST00000525131.5

  6. 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) ...

  7. 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) ...

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

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    119205845..119210583
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    UniProtKB/Swiss-Prot
    Q86UT5, Q8N6R4, Q8NAW7, Q8NEX7, Q9H5Z3

  2. XM_054369995.1 → XP_054225970.1  Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X3

  3. XM_054369994.1 → XP_054225969.1  Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X2

  4. XM_054369996.1 → XP_054225971.1  Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X4

    UniProtKB/TrEMBL
    E9PPZ1

  5. XM_054369997.1 → XP_054225972.1  Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X5

  6. XM_054369998.1 → XP_054225973.1  Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X6

  7. XM_054369999.1 → XP_054225974.1  Na(+)/H(+) exchange regulatory cofactor NHE-RF4 isoform X7

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q86UT5.2 GenPept UniProtKB/Swiss-Prot:Q86UT5

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