NHRF3_RABIT
ID NHRF3_RABIT Reviewed; 518 AA.
AC Q865P3;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 25-MAY-2022, entry version 86.
DE RecName: Full=Na(+)/H(+) exchange regulatory cofactor NHE-RF3;
DE Short=NHERF-3;
DE AltName: Full=CFTR-associated protein of 70 kDa;
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=CAP70, NHERF3;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND INTERACTION
RP WITH SLC26A3.
RX PubMed=15766278; DOI=10.1021/bi048828b;
RA Rossmann H., Jacob P., Baisch S., Hassoun R., Meier J., Natour D.,
RA Yahya K., Yun C., Biber J., Lackner K.J., Fiehn W., Gregor M., Seidler U.,
RA Lamprecht G.;
RT "The CFTR associated protein CAP70 interacts with the apical Cl-/HCO3-
RT exchanger DRA in rabbit small intestinal mucosa.";
RL Biochemistry 44:4477-4487(2005).
RN [2]
RP INTERACTION WITH SLC26A6.
RX PubMed=16141316; DOI=10.1073/pnas.0506578102;
RA Thomson R.B., Wang T., Thomson B.R., Tarrats L., Girardi A., Mentone S.,
RA Soleimani M., Kocher O., Aronson P.S.;
RT "Role of PDZK1 in membrane expression of renal brush border ion
RT exchangers.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:13331-13336(2005).
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, ECO:0000269|PubMed:15766278}.
CC -!- SUBUNIT: Interacts with PDZK1IP1 and ABCC2. Interacts (via PDZ domains
CC 1 and 3) with SCARB1 (C-terminal domain). Forms a heterodimeric complex
CC with SLC9A3R1. Interacts with AKAP2, BCR, CFTR, SLCO1A1, SLC22A12,
CC SLC22A4, SLC22A5, SLC9A3R2 and SLC17A1. Component of a complex,
CC composed of PDZK1, SYNGAP1, KLHL17 and NMDA receptors. Interacts (via
CC PDZ1 domain) directly with KLHL17; the interaction is important for
CC integrity of actin cytoskeleton structures in neurons. Interacts (via
CC C-terminal PDZ domain) with SLC9A3 (via C-terminal domain). Interacts
CC (via the first PDZ domain) with PTGIR (via non-isoprenylated C-
CC terminus) (By similarity). Binds to the C-terminal region of SLC26A3.
CC Interacts (via C-terminal PDZ domain) with SLC26A6 (via C-terminal
CC domain). {ECO:0000250, ECO:0000269|PubMed:15766278,
CC ECO:0000269|PubMed:16141316}.
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 -!- TISSUE SPECIFICITY: Highly expressed in the brush border membrane of
CC duodenal and ileal mucosa. {ECO:0000269|PubMed:15766278}.
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; AY204473; AAO34667.1; -; mRNA.
DR RefSeq; NP_001075620.1; NM_001082151.2.
DR AlphaFoldDB; Q865P3; -.
DR SMR; Q865P3; -.
DR STRING; 9986.ENSOCUP00000021164; -.
DR GeneID; 100008900; -.
DR KEGG; ocu:100008900; -.
DR CTD; 5174; -.
DR eggNOG; KOG3528; Eukaryota.
DR InParanoid; Q865P3; -.
DR OrthoDB; 880632at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; ISS:UniProtKB.
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 1: Evidence at protein level;
KW Cell membrane; Membrane; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..518
FT /note="Na(+)/H(+) exchange regulatory cofactor NHE-RF3"
FT /id="PRO_0000058290"
FT DOMAIN 9..90
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 135..215
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 243..323
FT /note="PDZ 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 378..458
FT /note="PDZ 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 499..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..518
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 108
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JJ40"
FT MOD_RES 148
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5T2W1"
FT MOD_RES 192
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 250
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 334
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 348
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 451
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 507
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 510
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 513
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
SQ SEQUENCE 518 AA; 56972 MW; 4493C0512771D466 CRC64;
MASTFNPREC KLSKEEGQNY GFFLRIEKDT EGHLVRVIEK GSPAEKAGLQ DGDRVLRING
VFVDKEEHMQ VVDLVRKSGN AVTLLVLDGN SYEKAVKKQV DLKELGQSRQ EADLRDENVA
PVMNGGVETW TQPRLCYLEK QGNSYGFSLK TVQGKKGVYM TDIIPQSVAM KAGVLADDHL
IEVNGENVED ASHEEVVEKV KKSGNRIVFL LVDKETEKRH SEQKIEFRRE AASLKLLPHQ
PRIVEMKKGS SGYGFYLKAG PEQRGQIIKD IDSGSPAEAA GLKNNDLVIA VNGKSVEALD
HDGVVELIKK GGDQTSLLVV DKEADSMYRL AHFSPFLYYQ SQELPNGSVT EVAAPTPVPP
EVSSPDPTEE VEDHKPKLCR LDKGENGYGF HLNAIRGLPG SFVKEVQKGS PADLAGLEDE
DIIIEVNGVN VLDEPYEKVV DRIQSSGDNV TLLVCGKKAY EYFQAKKIPI VSSMALPLAI
PADSQGMLAE LEYNLHEAKE RAHSTASNSS SNSEDTEL
