NHRF1_MACFA
ID NHRF1_MACFA Reviewed; 358 AA.
AC Q4R6G4;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 96.
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; ORFNames=QtsA-18078;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-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). Involved in the regulation of
CC phosphate reabsorption in the renal proximal tubules (By similarity).
CC {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=Translocates from the cytoplasm to the apical cell
CC membrane in a PODXL-dependent manner. Colocalizes with actin in
CC microvilli-rich apical regions of the syncytiotrophoblast. Present in
CC lipid rafts of T-cells. Colocalizes with CFTR at the midpiece of sperm
CC tail (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine residues. {ECO:0000250}.
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DR EMBL; AB169219; BAE01311.1; -; mRNA.
DR RefSeq; NP_001272109.1; NM_001285180.1.
DR AlphaFoldDB; Q4R6G4; -.
DR SMR; Q4R6G4; -.
DR STRING; 9541.XP_005584930.1; -.
DR GeneID; 101926883; -.
DR CTD; 9368; -.
DR VEuPathDB; HostDB:ENSMFAG00000043867; -.
DR eggNOG; KOG3528; Eukaryota.
DR OMA; NGQIHGH; -.
DR OrthoDB; 880632at2759; -.
DR Proteomes; UP000233100; Chromosome 16.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
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: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:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0097225; C:sperm midpiece; ISS:UniProtKB.
DR GO; GO:0017081; F:chloride channel regulator activity; ISS:UniProtKB.
DR GO; GO:0060090; F:molecular adaptor activity; IEA:InterPro.
DR GO; GO:0032782; P:bile acid secretion; ISS:UniProtKB.
DR GO; GO:0034635; P:glutathione transport; ISS:UniProtKB.
DR GO; GO:2000146; P:negative regulation of cell motility; ISS:UniProtKB.
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:0045859; P:regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0070293; P:renal absorption; ISS:UniProtKB.
DR GO; GO:0097291; P:renal phosphate ion absorption; ISS:UniProtKB.
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..358
FT /note="Na(+)/H(+) exchange regulatory cofactor NHE-RF1"
FT /id="PRO_0000301265"
FT DOMAIN 14..94
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 154..234
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 114..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 134..153
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..322
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..348
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 162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 280
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 290
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q28619"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70441"
FT MOD_RES 293
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P70441"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14745"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70441"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70441"
SQ SEQUENCE 358 AA; 38837 MW; 0939063A3539F3CE CRC64;
MSADAAAGAP LPRLCCLEKG PNGYGFHLHG EKGKLGQYIR LVEPGSPAEK AGLLAGDRLV
EVNGENVEKE THQQVVSRIR AALNAVRLLV VDPETDEQLQ KLGVQVREEL LRAQETPGQA
EPAAAAEAQG AGNENEPREA DKSHPEQRKL RPRLCTMKKG PSGYGFNLHS DKSKPGQFIR
SVDPDSPAEA SGLRAQDRIV EVNGVCMEGK QHGDVVSAIR AGGDETKLLV VDRETDEFFK
KCKVTPSQEH LNGPLPEPFT NGEIQKENSR EALAEAASES PRPTLVRSAS SDTSEELNSQ
DSPPKQDSTA PSSTSSSDPI LDFNISLAMA KERAHQKRSS KRAPQMDWSK KNELFSNL
