Q9JJ19
SS
Gene name |
Nherf1 (Nherf, Slc9a3r1) |
Protein name |
Na |
Names |
+/H, + exchange regulatory cofactor NHE-RF1 , NHERF-1 , Ezrin-radixin-moesin-binding phosphoprotein 50 , EBP50 , Regulatory cofactor of Na, +/H, + exchanger , Sodium-hydrogen exchanger regulatory factor 1 , Solute carrier family 9 isoform A3 regulatory factor 1 |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:59114 |
EC number |
|
Protein Class |
|
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 |
14-94 (PDZ1 domain);151-231 (PDZ2 domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for Q9JJ19
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q9JJ19-F1 | Predicted | AlphaFoldDB |
2 variants for Q9JJ19
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs8144880 | 105 | P>R | No | EVA | |
| rs197216786 | 145 | C>R | No | EVA |
1 associated diseases with Q9JJ19
[MIM: 617075]: Nasopharyngeal carcinoma, 3 (NPCA3)
A form of nasopharyngeal carcinoma, a malignant neoplasm that originates in the nasopharyngeal epithelium and includes 4 subtypes
Without disease ID
- A form of nasopharyngeal carcinoma, a malignant neoplasm that originates in the nasopharyngeal epithelium and includes 4 subtypes
6 regional properties for Q9JJ19
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 60 - 311 | IPR000719 |
| domain | Kinase associated domain 1 (KA1) | 744 - 793 | IPR001772 |
| active_site | Serine/threonine-protein kinase, active site | 178 - 190 | IPR008271 |
| domain | Ubiquitin-associated domain | 329 - 370 | IPR015940 |
| binding_site | Protein kinase, ATP binding site | 66 - 89 | IPR017441 |
| domain | Serine/threonine-protein kinase MARK 1-4, catalytic domain | 59 - 311 | IPR049508 |
Functions
17 GO annotations of cellular component
| Name | Definition |
|---|---|
| apical part of cell | The region of a polarized cell that forms a tip or is distal to a base. For example, in a polarized epithelial cell, the apical region has an exposed surface and lies opposite to the basal lamina that separates the epithelium from other tissue. |
| apical plasma membrane | The region of the plasma membrane located at the apical end of the cell. |
| brush border membrane | The portion of the plasma membrane surrounding the brush border. |
| 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. |
| extracellular region | The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite. |
| 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. |
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it. |
| 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. |
| perinuclear region of cytoplasm | Cytoplasm situated near, or occurring around, the nucleus. |
| plasma membrane protein complex | Any protein complex that is part of the plasma membrane. |
| ruffle | Projection at the leading edge of a crawling cell; the protrusions are supported by a microfilament meshwork. |
| sperm midpiece | The highly organized segment of the sperm flagellum which begins at the connecting piece and is characterized by the presence of 9 outer dense fibers (ODFs) that lie outside each of the 9 outer axonemal microtubule doublets and by a sheath of mitochondria that encloses the ODFs and the axoneme; the midpiece terminates about one-fourth of the way down the sperm flagellum at the annulus, which marks the beginning of the principal piece. |
| stereocilium | An actin-based protrusion from the apical surface of auditory and vestibular hair cells and of neuromast cells. These protrusions are supported by a bundle of cross-linked actin filaments (an actin cable), oriented such that the plus (barbed) ends are at the tip of the protrusion, capped by a tip complex which bridges to the plasma. Bundles of stereocilia act as mechanosensory organelles. |
| stereocilium tip | A distinct compartment at the tip of a stereocilium, distal to the site of attachment to the apical cell surface. It consists of a dense matrix bridging the barbed ends of the stereocilium actin filaments with the overlying plasma membrane, is dynamic compared to the shaft, and is required for stereocilium elongation. |
19 GO annotations of molecular function
| Name | Definition |
|---|---|
| beta-2 adrenergic receptor binding | Binding to a beta-2 adrenergic receptor. |
| beta-catenin binding | Binding to a catenin beta subunit. |
| channel activator activity | Direct interaction with a channel (binding or modification), resulting in its opening. A channel catalyzes energy-independent facilitated diffusion, mediated by passage of a solute through a transmembrane aqueous pore or channel. |
| chloride channel regulator activity | Binds to and modulates the activity of a chloride channel. |
| dopamine receptor binding | Binding to a dopamine receptor. |
| growth factor receptor binding | Binding to a growth factor receptor. |
| identical protein binding | Binding to an identical protein or proteins. |
| molecular adaptor activity | The binding activity of a molecule that brings together two or more molecules through a selective, non-covalent, often stoichiometric interaction, permitting those molecules to function in a coordinated way. |
| myosin II binding | Binding to a class II myosin, any member of the class of 'conventional' double-headed myosins that includes muscle myosin. |
| PDZ domain binding | Binding to a PDZ domain of a protein, a domain found in diverse signaling proteins. |
| phosphatase binding | Binding to a phosphatase. |
| protein domain specific binding | Binding to a specific domain of a protein. |
| protein self-association | Binding to a domain within the same polypeptide. |
| protein-containing complex binding | Binding to a macromolecular complex. |
| 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. |
| transmembrane transporter binding | Binding to a transmembrane transporter, a protein or protein complex that enables the transfer of a substance, usually a specific substance or a group of related substances, from one side of a membrane to the other. |
| type 2 metabotropic glutamate receptor binding | Binding to a type 2 metabotropic glutamate receptor. |
| type 3 metabotropic glutamate receptor binding | Binding to a type 3 metabotropic glutamate receptor. |
43 GO annotations of biological process
| Name | Definition |
|---|---|
| actin cytoskeleton organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins. |
| adenylate cyclase-activating dopamine receptor signaling pathway | An adenylate cyclase-activating G protein-coupled receptor signaling pathway initiated by dopamine binding to its receptor, and ending with the regulation of a downstream cellular process. |
| auditory receptor cell stereocilium organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a stereocilium. A stereocilium is an actin-based protrusion from the apical surface of auditory hair cells. |
| 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. |
| cerebrospinal fluid circulation | The neurological system process driven by motile cilia on ependymal cells of the brain by which cerebrospinal fluid circulates from the sites of secretion to the sites of absorption. In ventricular cavities, the flow is unidirectional and rostrocaudal, in subarachnoid spaces, the flow is multi-directional. |
| cilium organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a cilium, a specialized eukaryotic organelle that consists of a filiform extrusion of the cell surface. Each cilium is bounded by an extrusion of the cytoplasmic membrane, and contains a regular longitudinal array of microtubules, anchored basally in a centriole. |
| establishment of epithelial cell apical/basal polarity | The specification and formation of the apicobasal polarity of an epithelial cell. |
| establishment of Golgi localization | The directed movement of the Golgi to a specific location. |
| establishment of localization in cell | Any process, occuring in a cell, that localizes a substance or cellular component. This may occur via movement, tethering or selective degradation. |
| fibroblast migration | Cell migration that is accomplished by extension and retraction of a fibroblast pseudopodium. A fibroblast is a connective tissue cell which secretes an extracellular matrix rich in collagen and other macromolecules. |
| gamma-aminobutyric acid import | The directed movement of gamma-aminobutyric acid (GABA, 4-aminobutyrate) into a cell or organelle. |
| gland morphogenesis | The process in which the anatomical structures of a gland are generated and organized. |
| 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. |
| import across plasma membrane | The directed movement of some substance from outside of a cell, across the plasma membrane and into the cytosol. |
| intracellular phosphate ion homeostasis | A homeostatic process involved in the maintenance of a steady state level of phosphate ions within a cell. |
| maintenance of epithelial cell apical/basal polarity | The maintenance of the apicobasal polarity of an epithelial cell. |
| microvillus assembly | Formation of a microvillus, a thin cylindrical membrane-covered projection on the surface of a cell. |
| negative regulation of canonical Wnt signaling pathway | Any process that decreases the rate, frequency, or extent of the Wnt signaling pathway through beta-catenin, the series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes. |
| negative regulation of cell motility | Any process that stops, prevents, or reduces the frequency, rate or extent of cell motility. |
| negative regulation of cell population proliferation | Any process that stops, prevents or reduces the rate or extent of cell proliferation. |
| negative regulation of ERK1 and ERK2 cascade | Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. |
| negative regulation of fibroblast migration | Any process that decreases the rate, frequency or extent of fibroblast cell migration. Fibroblast cell migration is accomplished by extension and retraction of a pseudopodium. |
| negative regulation of mitotic cell cycle | Any process that stops, prevents or reduces the rate or extent of progression through the mitotic cell cycle. |
| 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. |
| negative regulation of sodium ion transport | Any process that decreases the frequency, rate or extent of the directed movement of sodium ions (Na+) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| nuclear migration | The directed movement of the nucleus to a specific location within a cell. |
| phospholipase C-activating dopamine receptor signaling pathway | A phospholipase C-activating receptor G protein-coupled receptor signaling pathway initiated by dopamine binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| plasma membrane organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of the plasma membrane. |
| positive regulation of intrinsic apoptotic signaling pathway | Any process that activates or increases the frequency, rate or extent of intrinsic apoptotic signaling pathway. |
| positive regulation of monoatomic ion transmembrane transport | Any process that activates or increases the frequency, rate or extent of the directed movement of ions from one side of a membrane to the other. |
| protein localization | Any process in which a protein is transported to, or maintained in, a specific location. |
| 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 cell shape | Any process that modulates the surface configuration of a cell. |
| regulation of cell size | Any process that modulates the size of a cell. |
| regulation of protein kinase activity | Any process that modulates the frequency, rate or extent of protein kinase activity. |
| regulation of renal phosphate excretion | Any process that modulates the frequency, rate or extent of renal phosphate excretion. |
| 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). |
| renal phosphate ion absorption | A renal system process in which phosphate ions are taken up from the collecting ducts and proximal and distal loops of the nephron. In non-mammalian species, absorption may occur in related structures. |
| renal sodium ion transport | The directed movement of sodium ions (Na+) by the renal system. |
| sensory perception of sound | The series of events required for an organism to receive an auditory stimulus, convert it to a molecular signal, and recognize and characterize the signal. Sonic stimuli are detected in the form of vibrations and are processed to form a sound. |
| sodium ion transport | The directed movement of sodium ions (Na+) into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| 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 |
| Q5ZM14 | NHERF1 | Na | Gallus gallus (Chicken) | 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 |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSADAAAGEP | LPRLCCLEKG | PNGYGFHLHG | EKGKVGQFIR | LVEPGSPAEK | SGLLAGDRLV |
| 70 | 80 | 90 | 100 | 110 | 120 |
| EVNGENVEKE | THQQVVSRIR | AALNAVRLLV | VDPETDEQLK | KLGVPIREEL | LRAQEKSEHT |
| 130 | 140 | 150 | 160 | 170 | 180 |
| EPPAAADTKK | AGDQNEAEKS | HLERCELRPR | LCTMKKGPNG | YGFNLHSDKS | KPGQFIRAVD |
| 190 | 200 | 210 | 220 | 230 | 240 |
| PDSPAEASGL | RAQDRIVEVN | GVCMEGKQHG | DVVSAIKAGG | DEAKLLVVDK | ETDEFFKKCR |
| 250 | 260 | 270 | 280 | 290 | 300 |
| VTPSQEHLDG | PLPEPFSNGE | IQKENSREAL | VEPASESPRP | ALARSASSDT | SEELNAQDSP |
| 310 | 320 | 330 | 340 | 350 | |
| KRHDSTEPSS | TSSSSDPILD | FNISLAVAKE | RAHQKRSSKR | APQMDWSKKN | ELFSNL |