NHRF1_BOVIN
ID NHRF1_BOVIN Reviewed; 368 AA.
AC Q3SZK8;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Na(+)/H(+) exchange regulatory cofactor NHE-RF1;
DE Short=NHERF-1;
DE AltName: Full=Ezrin-radixin-moesin-binding phosphoprotein 50;
DE Short=EBP50;
DE AltName: Full=Regulatory cofactor of Na(+)/H(+) exchanger;
DE AltName: Full=Sodium-hydrogen exchanger regulatory factor 1;
DE AltName: Full=Solute carrier family 9 isoform A3 regulatory factor 1;
GN Name=SLC9A3R1; Synonyms=NHERF, NHERF1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Scaffold protein that connects plasma membrane proteins with
CC members of the ezrin/moesin/radixin family and thereby helps to link
CC them to the actin cytoskeleton and to regulate their surface
CC expression. Necessary for recycling of internalized ADRB2. Was first
CC known to play a role in the regulation of the activity and subcellular
CC location of SLC9A3. Necessary for cAMP-mediated phosphorylation and
CC inhibition of SLC9A3. Involved in sperm capacitation. May participate
CC in the regulation of the chloride and bicarbonate homeostasis in
CC spermatozoa. May enhance Wnt signaling. May participate in HTR4
CC targeting to microvilli (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer, and heterodimer with SLC9A3R2. Binds the N-termini
CC of EZR, RDX and MSN. Binds the C-termini of PDGFRA, PDGFRB, ADRB2, NOS2
CC and CFTR. Binds ARHGAP17, EPI64, RACK1, OPRK1, GNAQ, CTNNB1 and PLCB3.
CC Binds PDZK1 (By similarity). Interacts with CLCN3. Binds the C-terminus
CC of PAG1. In resting T-cells, part of a PAG1-SLC9A3R1-MSN complex which
CC is disrupted upon TCR activation. Forms a complex with CFTR and SLC4A7.
CC Forms a complex with SLC4A7 and ATP6V1B1. Interacts with TRPC4 (via the
CC PDZ-binding domain). Directly interacts with HTR4 (By similarity).
CC Interacts (via the PDZ 1 domain) with PODXL (via the C-terminal PDZ-
CC binding motif DTHL); interaction is not detected in glomerular
CC epithelium cells. Interacts (via the PDZ 1 domain) with PODXL (via the
CC C-terminal PDZ-binding motif DTHL); the interaction take place early in
CC the secretory pathway and is necessary for its apical membrane sorting
CC (By similarity). Interacts with SLC26A3 (By similarity). Interacts with
CC MCC. Interacts with SLC34A1. Interacts (via the PDZ domains) with
CC SLC26A6 isoform 4 and isoform 5 (By similarity). Interacts (via PDZ
CC domains) with ACE2 (via PDZ-binding motif); the interaction may enhance
CC ACE2 membrane residence (By similarity). {ECO:0000250|UniProtKB:O14745,
CC ECO:0000250|UniProtKB:P70441}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Apical cell membrane
CC {ECO:0000250}. Endomembrane system {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Cell projection, filopodium {ECO:0000250}. Cell
CC projection, ruffle {ECO:0000250}. Cell projection, microvillus
CC {ECO:0000250}. Note=Colocalizes with actin in microvilli-rich apical
CC regions of the syncytiotrophoblast. Present in lipid rafts of T-cells.
CC Translocates from the cytoplasm to the apical cell membrane in a PODXL-
CC dependent manner. Colocalizes with CFTR at the midpiece of sperm tail
CC (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine residues. {ECO:0000250}.
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DR EMBL; BC102807; AAI02808.1; -; mRNA.
DR RefSeq; NP_001071320.1; NM_001077852.2.
DR AlphaFoldDB; Q3SZK8; -.
DR SMR; Q3SZK8; -.
DR STRING; 9913.ENSBTAP00000034568; -.
DR PaxDb; Q3SZK8; -.
DR PeptideAtlas; Q3SZK8; -.
DR PRIDE; Q3SZK8; -.
DR Ensembl; ENSBTAT00000034682; ENSBTAP00000034568; ENSBTAG00000011382.
DR GeneID; 505242; -.
DR KEGG; bta:505242; -.
DR CTD; 9368; -.
DR VEuPathDB; HostDB:ENSBTAG00000011382; -.
DR VGNC; VGNC:34941; SLC9A3R1.
DR eggNOG; KOG3528; Eukaryota.
DR GeneTree; ENSGT00950000182849; -.
DR HOGENOM; CLU_038627_1_0_1; -.
DR InParanoid; Q3SZK8; -.
DR OMA; NGQIHGH; -.
DR OrthoDB; 880632at2759; -.
DR TreeFam; TF350449; -.
DR Proteomes; UP000009136; Chromosome 19.
DR Bgee; ENSBTAG00000011382; Expressed in metanephros cortex and 104 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0071944; C:cell periphery; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:GOC.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005902; C:microvillus; ISS:UniProtKB.
DR GO; GO:0031528; C:microvillus membrane; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0097225; C:sperm midpiece; ISS:UniProtKB.
DR GO; GO:0032426; C:stereocilium tip; IEA:Ensembl.
DR GO; GO:0031698; F:beta-2 adrenergic receptor binding; IEA:Ensembl.
DR GO; GO:0008013; F:beta-catenin binding; IEA:Ensembl.
DR GO; GO:0017081; F:chloride channel regulator activity; ISS:UniProtKB.
DR GO; GO:0050780; F:dopamine receptor binding; IEA:Ensembl.
DR GO; GO:0070851; F:growth factor receptor binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0030165; F:PDZ domain binding; IEA:Ensembl.
DR GO; GO:0019902; F:phosphatase binding; IEA:Ensembl.
DR GO; GO:0043621; F:protein self-association; IEA:Ensembl.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0031799; F:type 2 metabotropic glutamate receptor binding; IEA:Ensembl.
DR GO; GO:0031800; F:type 3 metabotropic glutamate receptor binding; IEA:Ensembl.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0007191; P:adenylate cyclase-activating dopamine receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0060088; P:auditory receptor cell stereocilium organization; IEA:Ensembl.
DR GO; GO:0032782; P:bile acid secretion; ISS:UniProtKB.
DR GO; GO:0030643; P:cellular phosphate ion homeostasis; IEA:Ensembl.
DR GO; GO:0090660; P:cerebrospinal fluid circulation; IEA:Ensembl.
DR GO; GO:0044782; P:cilium organization; IEA:Ensembl.
DR GO; GO:0045198; P:establishment of epithelial cell apical/basal polarity; IEA:Ensembl.
DR GO; GO:0051683; P:establishment of Golgi localization; IEA:Ensembl.
DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl.
DR GO; GO:0022612; P:gland morphogenesis; IEA:Ensembl.
DR GO; GO:0034635; P:glutathione transport; ISS:UniProtKB.
DR GO; GO:0045199; P:maintenance of epithelial cell apical/basal polarity; IEA:Ensembl.
DR GO; GO:0030033; P:microvillus assembly; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:2000146; P:negative regulation of cell motility; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0010764; P:negative regulation of fibroblast migration; IEA:Ensembl.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0032416; P:negative regulation of sodium:proton antiporter activity; IEA:Ensembl.
DR GO; GO:0007097; P:nuclear migration; IEA:Ensembl.
DR GO; GO:0060158; P:phospholipase C-activating dopamine receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0007009; P:plasma membrane organization; IEA:Ensembl.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0072659; P:protein localization to plasma membrane; IBA:GO_Central.
DR GO; GO:0008360; P:regulation of cell shape; IEA:Ensembl.
DR GO; GO:0008361; P:regulation of cell size; IEA:Ensembl.
DR GO; GO:0045859; P:regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:1903402; P:regulation of renal phosphate excretion; IEA:Ensembl.
DR GO; GO:0070293; P:renal absorption; ISS:UniProtKB.
DR GO; GO:0097291; P:renal phosphate ion absorption; IEA:Ensembl.
DR GO; GO:0003096; P:renal sodium ion transport; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 2.30.42.10; -; 2.
DR InterPro; IPR015098; EBP50_C-term.
DR InterPro; IPR031199; NHERF-1.
DR InterPro; IPR017300; NHERF-1/NHERF-2.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR PANTHER; PTHR14191:SF7; PTHR14191:SF7; 1.
DR Pfam; PF09007; EBP50_C; 1.
DR Pfam; PF00595; PDZ; 2.
DR PIRSF; PIRSF037866; EBP50; 1.
DR SMART; SM00228; PDZ; 2.
DR SUPFAM; SSF50156; SSF50156; 2.
DR PROSITE; PS50106; PDZ; 2.
PE 2: Evidence at transcript level;
KW Acetylation; Cell membrane; Cell projection; Cytoplasm; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Wnt signaling pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT CHAIN 2..368
FT /note="Na(+)/H(+) exchange regulatory cofactor NHE-RF1"
FT /id="PRO_0000301264"
FT DOMAIN 14..94
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 162..242
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 113..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 253..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 291..332
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 341..358
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 288
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28619"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70441"
FT MOD_RES 301
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P70441"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70441"
FT MOD_RES 310
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70441"
SQ SEQUENCE 368 AA; 39603 MW; 8215AB11957F3395 CRC64;
MSADAGAGAP LPRLCCLEKG PNGYGFHLHG EKGKVGQYIR LVEPGSPAEK SGLLAGDRLV
EVNGENVEKE THQQVVNRIR AALNSVRLLV VDPETDERLQ KLGVQVREEM LRAQEGPGQA
EPPAAAAEER GAGGENEPPA AAPEPREAEQ SPQERRELRP RLCAMKKGPN GYGFNLHSDK
SKPGQFIRAV DPDSPAEASG LRAQDRIVEV NGVCVEGKPH GEVVSAIKAG GDEAKLLVVD
RETDEFFKKC KVIPSQEHLQ GPLPEPITNG EIEKENSPEA LAETASESPM PPLARTASSD
TSEELNSQDS PKKQDSTAPS STSSSSSDPV LDFSISLAVA KERAHQKRVS KRAPQMDWSK
KNELFSNL
