Q3SZK8

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
Bos taurus (Bovine)
KEGG Pathway
bta:505242
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)

250-368 (CT domain, EB domain, and PDZ-binding motif) SS

Target domain

14-94 (PDZ1 domain);162-242 (PDZ2 domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q3SZK8

Entry ID Method Resolution Chain Position Source
AF-Q3SZK8-F1 Predicted AlphaFoldDB

239 variants for Q3SZK8

Variant ID(s) Position Change Description Diseaes Association Provenance
rs441838802 2 S>G No EVA
rs483181917 7 A>T No EVA
rs463105002 8 G>V No EVA
rs470811788 10 P>S No EVA
rs460655363 11 L>Q No EVA
rs475143121 14 L>F No EVA
rs438234188 16 C>* No EVA
rs455035353 16 C>R No EVA
rs476260484 17 L>P No EVA
rs456225074 18 E>G No EVA
rs432711023 20 G>C No EVA
rs432711023 20 G>R No EVA
rs447307377 22 N>S No EVA
rs448181284 24 Y>* No EVA
rs468510661 24 Y>D No EVA
rs482870241 26 F>L No EVA
rs462968336 27 H>P No EVA
rs446139611 28 L>P No EVA
rs446139611 28 L>R No EVA
rs477339851 29 H>D No EVA
rs460363020 29 H>R No EVA
rs475106258 31 E>G No EVA
rs444552490 33 G>R No EVA
rs456138600 35 V>E No EVA
rs456138600 35 V>G No EVA
rs432821725 36 G>S No EVA
rs453715343 37 Q>P No EVA
rs468397181 38 Y>* No EVA
rs433606319 38 Y>F No EVA
rs448375433 39 I>L No EVA
rs469184345 39 I>M No EVA
rs437749856 39 I>N No EVA
rs477300590 40 R>P No EVA
rs445830268 40 R>W No EVA
rs446753503 42 V>G No EVA
rs461575101 43 E>D No EVA
rs481230690 43 E>G No EVA
rs444751596 44 P>A No EVA
rs470679189 48 A>T No EVA
rs453827124 49 E>G No EVA
rs439989123 50 K>E No EVA
rs474634746 51 S>A No EVA
rs469297698 54 L>P No EVA
rs452189501 55 A>G No EVA
rs466862991 56 G>A No EVA
rs466862991 56 G>V No EVA
rs450830727 57 D>E No EVA
rs467769360 57 D>V No EVA
rs481449816 57 D>Y No EVA
rs482559930 59 L>I No EVA
rs459225959 59 L>P No EVA
rs459225959 59 L>R No EVA
rs480017522 60 V>G No EVA
rs438975343 60 V>M No EVA
rs440151319 61 E>G No EVA
rs460197178 61 E>K No EVA
rs474747335 62 V>A No EVA
rs474747335 62 V>G No EVA
rs444041585 63 N>D No EVA
rs444041585 63 N>H No EVA
rs452299894 63 N>K No EVA
rs475706571 63 N>T No EVA
rs466627593 64 G>D No EVA
rs432120183 64 G>R No EVA
rs467884172 65 E>G No EVA
rs436475360 65 E>Q No EVA
rs450866222 66 N>D No EVA
rs465622559 66 N>K No EVA
rs437181561 66 N>T No EVA
rs445575604 67 V>A No EVA
rs445575604 67 V>G No EVA
rs459912079 68 E>G No EVA
rs449546734 69 K>E No EVA
rs443978989 70 E>G No EVA
rs461008327 70 E>K No EVA
rs458649133 71 T>N No EVA
rs475424128 71 T>P No EVA
rs438639715 72 H>L No EVA
rs438639715 72 H>P No EVA
rs438639715 72 H>R No EVA
rs452979697 74 Q>K No EVA
rs436231487 74 Q>P No EVA
rs436231487 74 Q>R No EVA
rs474278154 75 V>A No EVA
rs474278154 75 V>G No EVA
rs437152175 76 V>A No EVA
rs437152175 76 V>G No EVA
rs457376937 76 V>L No EVA
rs445281435 77 N>K No EVA
rs465383460 77 N>S No EVA
rs465383460 77 N>T No EVA
rs435070282 78 R>G No EVA
rs435070282 78 R>S No EVA
rs449421923 79 I>L No EVA
rs480887682 80 R>P No EVA
rs450522116 81 A>G No EVA
rs481752963 82 A>P No EVA
rs481752963 82 A>S No EVA
rs458361547 82 A>V No EVA
rs438401034 83 L>H No EVA
rs438401034 83 L>P No EVA
rs473105828 84 N>D No EVA
rs459485563 84 N>S No EVA
rs459485563 84 N>T No EVA
rs442571202 86 V>G No EVA
rs474022713 88 L>P No EVA
rs474022713 88 L>R No EVA
rs457406185 89 L>P No EVA
rs457406185 89 L>Q No EVA
rs437256741 90 V>G No EVA
rs471922815 91 V>D No EVA
rs471922815 91 V>G No EVA
rs451722865 92 D>A No EVA
rs451722865 92 D>G No EVA
rs434778133 94 E>D No EVA
rs466428975 95 T>A No EVA
rs455984959 96 D>G No EVA
rs455984959 96 D>V No EVA
rs435757797 97 E>V No EVA
rs450298247 100 Q>P No EVA
rs481716045 101 K>E No EVA
rs464943298 102 L>W No EVA
rs444753175 103 G>A No EVA
rs479222240 105 Q>R No EVA
rs459610951 106 V>L No EVA
rs442713792 107 R>G No EVA
rs480576382 107 R>P No EVA
rs443493854 108 E>A No EVA
rs463502138 108 E>Q No EVA
rs471846953 109 E>* No EVA
rs451835474 109 E>G No EVA
rs455748871 110 M>I No EVA
rs441210225 110 M>L No EVA
rs472608650 110 M>R No EVA
rs456672089 114 Q>K No EVA
rs479181575 119 Q>E No EVA
rs479181575 119 Q>K No EVA
rs137635101 119 Q>R No EVA
rs134424759 120 A>G No EVA
rs465701069 120 A>P No EVA
rs480562618 121 E>D No EVA
rs448899978 121 E>V No EVA
rs463672107 122 P>L No EVA
rs443406283 129 E>Q No EVA
rs478016737 138 P>A No EVA
rs458206397 138 P>R No EVA
rs441319472 143 P>Q No EVA
rs450602394 169 P>S No EVA
rs433778983 193 D>E No EVA
rs468660954 205 D>A No EVA
rs448515429 208 V>L No EVA
rs480845210 212 G>R No EVA
rs460810804 213 V>A No EVA
rs460810804 213 V>G No EVA
rs481967499 214 C>G No EVA
rs481967499 214 C>S No EVA
rs458679347 214 C>S No EVA
rs438589647 215 V>L No EVA
rs473452162 216 E>G No EVA
rs442815584 219 P>L No EVA
rs474168992 221 G>R No EVA
rs457360178 222 E>G No EVA
rs437482246 223 V>A No EVA
rs437482246 223 V>G No EVA
rs451760146 225 S>C No EVA
rs472177469 225 S>P No EVA
rs434985326 226 A>D No EVA
rs466599706 227 I>L No EVA
rs466599706 227 I>V No EVA
rs446479199 230 G>D No EVA
rs436086187 232 D>E No EVA
rs467192608 233 E>A No EVA
rs450447851 238 V>G No EVA
rs482130591 239 V>A No EVA
rs482130591 239 V>E No EVA
rs482130591 239 V>G No EVA
rs458860626 240 D>E No EVA
rs444956384 241 R>G No EVA
rs479678482 241 R>S No EVA
rs459566991 242 E>D No EVA
rs442926248 244 D>E No EVA
rs474336528 246 F>V No EVA
rs443648859 250 C>* No EVA
rs472033030 251 K>Q No EVA
rs452003973 252 V>M No EVA
rs435106936 254 P>H No EVA
rs472823306 256 Q>P No EVA
rs472823306 256 Q>R No EVA
rs455817163 257 E>D No EVA
rs436049566 258 H>D No EVA
rs467306865 258 H>P No EVA
rs467306865 258 H>R No EVA
rs450359945 261 G>C No EVA
rs433199500 280 A>P No EVA
rs464499981 281 L>V No EVA
rs453941774 285 A>G No EVA
rs468438615 286 S>Y No EVA
rs448668772 287 E>D No EVA
rs483338828 288 S>T No EVA
rs469556555 290 M>L No EVA
rs446229731 291 P>R No EVA
rs457846786 292 P>A No EVA
rs440971819 293 L>V No EVA
rs478588149 294 A>T No EVA
rs441888886 299 S>R No EVA
rs476545347 300 D>A No EVA
rs476545347 300 D>V No EVA
rs108989244 301 T>A No EVA
rs439376995 302 S>G No EVA
rs470875354 302 S>R No EVA
rs454060001 303 E>A No EVA
rs454060001 303 E>G No EVA
rs434088540 304 E>G No EVA
rs137818124 309 D>A No EVA
rs468804686 322 T>S No EVA
rs445610787 322 T>S No EVA
rs460293166 323 S>A No EVA
rs446572832 323 S>Y No EVA
rs481240342 327 S>A No EVA
rs461145024 327 S>C No EVA
rs444522714 328 D>A No EVA
rs458890522 332 D>N No EVA
rs438836513 335 I>S No EVA
rs443128973 337 L>P No EVA
rs474417343 338 A>G No EVA
rs434617052 339 V>M No EVA
rs457516007 344 A>D No EVA
rs437647348 347 K>T No EVA
rs468917211 348 R>G No EVA
rs381149481 349 V>I No EVA
rs431977391 359 S>C No EVA
rs466433856 360 K>Q No EVA
rs446723464 360 K>R No EVA
rs481425170 362 N>I No EVA
rs467542444 363 E>D No EVA
rs450607670 365 F>V No EVA
rs482280434 367 N>H No EVA
rs459054247 369 L>R No EVA
rs438948887 369 L>W No EVA

No associated diseases with Q3SZK8

3 regional properties for Q3SZK8

Type Name Position InterPro Accession
domain PDZ domain 114 - 194 IPR001478-1
domain PDZ domain 198 - 273 IPR001478-2
domain Peptidase M50 88 - 206 IPR008915

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Apical cell membrane
  • Endomembrane system ; Peripheral membrane protein
  • Cell projection, filopodium
  • Cell projection, ruffle
  • Cell projection, microvillus
  • Colocalizes with actin in microvilli-rich apical regions of the syncytiotrophoblast
  • Present in lipid rafts of T-cells
  • Translocates from the cytoplasm to the apical cell membrane in a PODXL-dependent manner
  • Colocalizes with CFTR at the midpiece of sperm tail (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

14 GO annotations of cellular component

Name Definition
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.
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 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.

14 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.
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 self-association Binding to a domain within the same polypeptide.
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.
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.

37 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.
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.
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.
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.
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.
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
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
Q9JJ19 Nherf1 Na Rattus norvegicus (Rat) SS
Q9JJ40 Pdzk1 Na(+)/H(+) exchange regulatory cofactor NHE-RF3 Rattus norvegicus (Rat) PR
10 20 30 40 50 60
MSADAGAGAP LPRLCCLEKG PNGYGFHLHG EKGKVGQYIR LVEPGSPAEK SGLLAGDRLV
70 80 90 100 110 120
EVNGENVEKE THQQVVNRIR AALNSVRLLV VDPETDERLQ KLGVQVREEM LRAQEGPGQA
130 140 150 160 170 180
EPPAAAAEER GAGGENEPPA AAPEPREAEQ SPQERRELRP RLCAMKKGPN GYGFNLHSDK
190 200 210 220 230 240
SKPGQFIRAV DPDSPAEASG LRAQDRIVEV NGVCVEGKPH GEVVSAIKAG GDEAKLLVVD
250 260 270 280 290 300
RETDEFFKKC KVIPSQEHLQ GPLPEPITNG EIEKENSPEA LAETASESPM PPLARTASSD
310 320 330 340 350 360
TSEELNSQDS PKKQDSTAPS STSSSSSDPV LDFSISLAVA KERAHQKRVS KRAPQMDWSK
KNELFSNL