NHRF3_BOVIN
ID NHRF3_BOVIN Reviewed; 520 AA.
AC Q3T0X8;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Na(+)/H(+) exchange regulatory cofactor NHE-RF3;
DE Short=NHERF-3;
DE AltName: Full=Na(+)/H(+) exchanger regulatory factor 3;
DE AltName: Full=PDZ domain-containing protein 1;
DE AltName: Full=Sodium-hydrogen exchanger regulatory factor 3;
GN Name=PDZK1; Synonyms=NHERF3, PDZD1;
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: A scaffold protein that connects plasma membrane proteins and
CC regulatory components, regulating their surface expression in
CC epithelial cells apical domains. May be involved in the coordination of
CC a diverse range of regulatory processes for ion transport and second
CC messenger cascades. In complex with SLC9A3R1, may cluster proteins that
CC are functionally dependent in a mutual fashion and modulate the
CC trafficking and the activity of the associated membrane proteins. May
CC play a role in the cellular mechanisms associated with multidrug
CC resistance through its interaction with ABCC2 and PDZK1IP1. May
CC potentiate the CFTR chloride channel activity. Required for normal
CC cell-surface expression of SCARB1. Plays a role in maintaining normal
CC plasma cholesterol levels via its effects on SCARB1. Plays a role in
CC the normal localization and function of the chloride-anion exchanger
CC SLC26A6 to the plasma membrane in the brush border of the proximal
CC tubule of the kidney. May be involved in the regulation of proximal
CC tubular Na(+)-dependent inorganic phosphate cotransport therefore
CC playing an important role in tubule function (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PDZK1IP1 and ABCC2. Binds to the C-terminal
CC region of SLC26A3. Interacts (via PDZ domains 1 and 3) with SCARB1 (C-
CC terminal domain). Forms a heterodimeric complex with SLC9A3R1.
CC Interacts with AKAP2, BCR, CFTR, SLCO1A1, SLC22A12, SLC22A4, SLC22A5,
CC SLC9A3R2 and SLC17A1. Component of a complex, composed of PDZK1,
CC SYNGAP1, KLHL17 and NMDA receptors. Interacts (via PDZ1 domain)
CC directly with KLHL17; the interaction is important for integrity of
CC actin cytoskeleton structures in neurons. Interacts (via C-terminal PDZ
CC domain) with SLC26A6 (via C-terminal domain). Interacts (via C-terminal
CC PDZ domain) with SLC9A3 (via C-terminal domain). Interacts (via the
CC first PDZ domain) with PTGIR (via non-isoprenylated C-terminus) (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q9JJ40};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q9JJ40}. Cell
CC membrane {ECO:0000250|UniProtKB:Q9JIL4}. Note=Associated with
CC peripheral membranes. Localizes to the apical compartment of proximal
CC tubular cells and to sinusoidal liver membranes.
CC {ECO:0000250|UniProtKB:Q9JJ40}.
CC -!- DOMAIN: The PDZ 2 and 3 domains seem to be involved in the interaction
CC with SLC26A3. {ECO:0000250}.
CC -!- DOMAIN: Interaction with the C-terminus of CFTR could be mediated
CC through independent binding of PDZ 1, 3 and 4 domains. {ECO:0000250}.
CC -!- DOMAIN: The PDZ 1 and 3 domains seem to be involved in the interaction
CC with SLCO1A1. {ECO:0000250}.
CC -!- DOMAIN: The PDZ 1 domain interacts with BCR. {ECO:0000250}.
CC -!- DOMAIN: The PDZ 2 and 4 domains do not interact with the C-terminal
CC region of SCARB1. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the NHER family. {ECO:0000305}.
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DR EMBL; BC102213; AAI02214.1; -; mRNA.
DR RefSeq; NP_001029783.1; NM_001034611.2.
DR RefSeq; XP_005204046.1; XM_005203989.3.
DR RefSeq; XP_005204047.1; XM_005203990.3.
DR AlphaFoldDB; Q3T0X8; -.
DR SMR; Q3T0X8; -.
DR STRING; 9913.ENSBTAP00000007638; -.
DR PaxDb; Q3T0X8; -.
DR GeneID; 534439; -.
DR KEGG; bta:534439; -.
DR CTD; 5174; -.
DR eggNOG; KOG3528; Eukaryota.
DR HOGENOM; CLU_031712_1_0_1; -.
DR InParanoid; Q3T0X8; -.
DR OrthoDB; 880632at2759; -.
DR TreeFam; TF350449; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0043495; F:protein-membrane adaptor activity; IBA:GO_Central.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IBA:GO_Central.
DR GO; GO:0044070; P:regulation of anion transport; ISS:UniProtKB.
DR Gene3D; 2.30.42.10; -; 4.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR Pfam; PF00595; PDZ; 3.
DR Pfam; PF17820; PDZ_6; 1.
DR SMART; SM00228; PDZ; 4.
DR SUPFAM; SSF50156; SSF50156; 4.
DR PROSITE; PS50106; PDZ; 4.
PE 2: Evidence at transcript level;
KW Cell membrane; Membrane; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..520
FT /note="Na(+)/H(+) exchange regulatory cofactor NHE-RF3"
FT /id="PRO_0000246785"
FT DOMAIN 9..90
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 133..214
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 242..322
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 377..457
FT /note="PDZ 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 352..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 472..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 487..507
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 108
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JJ40"
FT MOD_RES 147
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T2W1"
FT MOD_RES 191
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 347
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 450
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 491
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 509
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 511
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 512
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 513
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 515
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
SQ SEQUENCE 520 AA; 57175 MW; AA770CBACF0326E5 CRC64;
MASTFNPREC KLTKQEGNSY GFFLRIEKDT DGHLVRVIEK GSPAEKAGLQ DGDRVLRING
VFVDKEEHMQ VVDLVRKSGN SVTLLVLDGD SYEKAMKKQV DLKALGQSQE PSLNDKKAPS
VMNGGAQMWM QPRLCYLVKE GGSYGFSLKT VQGKNGVYMT DIKPQGVAMK AGVLADDHLI
EVNGENVEDA SHEEVVEKVK KSGSRVTFLL VDKETDKHHS EQKIKVKRET ASLKLLPCQP
RVVEMKKGSN GYGFYLRESP EQKGQIIKDI DPKSPAEKAG LKNNDLVVAV NGKSVESLDH
DSVVEMIRKG GDQTSLLVVD KETDNIYKLA GFSPFFYYQS QELPNGSVKE VPAPTPAPLE
VSSPETTEEV GDHKPKLCRL ARGEDGYGFH LNAVRGQPGS FVKEVQKGGP ADLAGLEDED
VIIEVNGVNM LDESYEKVVD RIQSSGKTVT LLVCGKKAYD YFQAKKIPIV SSMADPLDDD
PDPDEGRLEG SEQNSHMAEE RERAHSTASH SSSNSEDTEM
