Descriptions

The mammalian Na+/H+ exchange regulatory factor 1 (NHERF1) is a multidomain scaffolding protein essential for regulating the intracellular trafficking and macromolecular assembly of transmembrane ion channels and receptors. NHERF1 is held in an autoinhibited state through intramolecular interactions between PDZ2 and the CT domain that also includes a C-terminal PDZ-binding motif (-SNL). A central feature of NHERF1 is its binding to ezrin and to other ezrin-radixin-moesin (ERM) proteins, forming a communication bridge between plasma membrane proteins and the actin cytoskeleton ezrin modulates the PDZ domains of NHERF1 to assemble multiprotein complexes in a cooperative fashion. Upon binding to ezrin, the intramolecular domain-domain interaction is released.

Autoinhibitory domains (AIDs)

Target domain

13-93 (PDZ1 domain);135-215 (PDZ2 domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q5ZM14

Entry ID Method Resolution Chain Position Source
AF-Q5ZM14-F1 Predicted AlphaFoldDB

No variants for Q5ZM14

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q5ZM14

No associated diseases with Q5ZM14

6 regional properties for Q5ZM14

Type Name Position InterPro Accession
domain SNF2, N-terminal 49 - 327 IPR000330
domain Helicase, C-terminal domain-like 348 - 513 IPR001650
conserved_site DNA/RNA helicase, ATP-dependent, DEAH-box type, conserved site 169 - 178 IPR002464
domain Macro domain 704 - 897 IPR002589
domain Helicase superfamily 1/2, ATP-binding domain 42 - 230 IPR014001
domain SNF2/RAD5-like, C-terminal helicase domain 346 - 470 IPR049730

Functions

Description
EC Number
Subcellular Localization
  • Endomembrane system; Peripheral membrane protein
  • Cell projection, filopodium
  • Cell projection, ruffle
  • Cell projection, microvillus
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

8 GO annotations of cellular component

Name Definition
apical plasma membrane The region of the plasma membrane located at the apical end of the cell.
cell periphery The broad region around and including the plasma membrane of a cell, encompassing the cell cortex (inside the cell), the plasma membrane, and any external encapsulating structures.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
endomembrane system A collection of membranous structures involved in transport within the cell. The main components of the endomembrane system are endoplasmic reticulum, Golgi bodies, vesicles, cell membrane and nuclear envelope. Members of the endomembrane system pass materials through each other or though the use of vesicles.
filopodium Thin, stiff, actin-based protrusion extended by the leading edge of a motile cell such as a crawling fibroblast or amoeba, or an axonal or dendritic growth cone, or a dendritic shaft.
microvillus Thin cylindrical membrane-covered projections on the surface of an animal cell containing a core bundle of actin filaments. Present in especially large numbers on the absorptive surface of intestinal cells.
microvillus membrane The portion of the plasma membrane surrounding a microvillus.
ruffle Projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork.

3 GO annotations of molecular function

Name Definition
chloride channel regulator activity Binds to and modulates the activity of a chloride channel.
protein-membrane adaptor activity The binding activity of a molecule that brings together a protein or a protein complex with a membrane, or bringing together two membranes, either via membrane lipid binding or by interacting with a membrane protein, to establish or maintain the localization of the protein, protein complex or organelle.
signaling receptor binding Binding to one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.

9 GO annotations of biological process

Name Definition
bile acid secretion The regulated release of bile acid, composed of any of a group of steroid carboxylic acids occurring in bile, by a cell or a tissue.
glutathione transport The directed movement of glutathione, the tripeptide glutamylcysteinylglycine, into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
negative regulation of cell motility Any process that stops, prevents, or reduces the frequency, rate or extent of cell motility.
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction Any process that stops, prevents, or reduces the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B.
negative regulation of platelet-derived growth factor receptor signaling pathway Any process that stops, prevents, or reduces the frequency, rate or extent of the platelet-derived growth factor receptor signaling pathway.
protein localization to plasma membrane A process in which a protein is transported to, or maintained in, a specific location in the plasma membrane.
regulation of protein kinase activity Any process that modulates the frequency, rate or extent of protein kinase activity.
renal absorption A renal system process in which water, ions, glucose and proteins are taken up from the collecting ducts, glomerulus and proximal and distal loops of the nephron. In non-mammalian species, absorption may occur in related structures (e.g. protein absorption is observed in nephrocytes in Drosophila, see PMID:23264686).
Wnt signaling pathway The series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell and ending with a change in cell state.

11 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q3SZK8 NHERF1 Na Bos taurus (Bovine) SS
Q24008 inaD Inactivation-no-after-potential D protein Drosophila melanogaster (Fruit fly) PR
Q9Y6N9 USH1C Harmonin Homo sapiens (Human) PR
Q86UT5 PDZD3 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 Homo sapiens (Human) PR
O14745 SLC9A3R1 Na(+)/H(+) exchange regulatory cofactor NHE-RF1 Homo sapiens (Human) EV
Q99MJ6 Pdzd3 Na(+)/H(+) exchange regulatory cofactor NHE-RF4 Mus musculus (Mouse) PR
Q9JIL4 Pdzk1 Na(+)/H(+) exchange regulatory cofactor NHE-RF3 Mus musculus (Mouse) PR
Q0QWG9 Grid2ip Delphilin Mus musculus (Mouse) PR
P70441 Slc9a3r1 Na(+)/H(+) exchange regulatory cofactor NHE-RF1 Mus musculus (Mouse) PR
Q9JJ40 Pdzk1 Na(+)/H(+) exchange regulatory cofactor NHE-RF3 Rattus norvegicus (Rat) PR
Q9JJ19 Nherf1 Na Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MSSAPPGPAA PRLCCMEKGP DGYGFHLHGE KGKPGQYIRL VEAGSPAERS GLRAGDRLLE
70 80 90 100 110 120
VDGTNVERES HQQVVERIRA AAGAVRLLVV QPQPEEQPPK THSDPDGEAQ REPPAAETPA
130 140 150 160 170 180
AERSGPEERE LRPRLCRIKK GPNGYGFNLH SEKSRPGQYV RAVDPDSPAE AAGLRAQDRI
190 200 210 220 230 240
VEVNGTSVEG KQHADVVAAI KAGGDETKLL VVGVLADEFF KKCRVVPSEA HLAGPLPEPM
250 260 270 280 290 300
ANGDVEKENG GEPRLNSVSE RPPSPALATS PEGSETHSEP DTQEGDKRSS APSSLLDLDI
310 320 330
PLAVAKERAH QKRTSKRAPQ MDWSKKNELF SNL