NHRF3_PONAB
ID NHRF3_PONAB Reviewed; 519 AA.
AC Q5RCF7; Q5R7M6; Q5RF44;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 25-MAY-2022, entry version 80.
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;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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; CR857317; CAH89613.1; -; mRNA.
DR EMBL; CR858313; CAH90550.1; -; mRNA.
DR EMBL; CR860088; CAH92234.1; -; mRNA.
DR RefSeq; NP_001126306.1; NM_001132834.1.
DR RefSeq; NP_001128743.1; NM_001135271.1.
DR AlphaFoldDB; Q5RCF7; -.
DR SMR; Q5RCF7; -.
DR STRING; 9601.ENSPPYP00000001092; -.
DR GeneID; 100173285; -.
DR GeneID; 100189637; -.
DR KEGG; pon:100173285; -.
DR CTD; 5174; -.
DR eggNOG; KOG3528; Eukaryota.
DR InParanoid; Q5RCF7; -.
DR OrthoDB; 880632at2759; -.
DR Proteomes; UP000001595; 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 2: Evidence at transcript level;
KW Cell membrane; Membrane; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..519
FT /note="Na(+)/H(+) exchange regulatory cofactor NHE-RF3"
FT /id="PRO_0000058289"
FT DOMAIN 9..90
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 134..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 347..374
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 473..519
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 486..504
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 505..519
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 508
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 512
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT MOD_RES 514
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JIL4"
FT CONFLICT 101
FT /note="D -> V (in Ref. 1; CAH92234)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="D -> G (in Ref. 1; CAH90550)"
FT /evidence="ECO:0000305"
FT CONFLICT 494
FT /note="H -> P (in Ref. 1; CAH90550)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 519 AA; 57148 MW; B134066B9FF046EA CRC64;
MTSTFNPREC KLSKQEGQNY GFFLRIEKDT EGHLVRVVEK GSPAEKAGLQ DGDRVLRIND
VFVDKEEHMQ VVDLVRKSGN SVTLLVLDGD SYEKAVKTRV DLKELGQRQK EQGLSDNTLS
PVMNGGVQTW TQPRLCYLVK EGGSYGFSLK TVQGKKGVYM TDITPQGVAM KAGVLADDHL
IEVNGENVED ASHEQVVEKV KKSGSRVMFL LVDKETDKHH VEQKIQFKRE TASLKLLPHQ
PRIVEMKKGS NGYGFYLRAG SEQKGQIIKD IDSGSPAEEA GLKNNDLVVA VNGESVETLD
HDSVVEMIRK GGDQTSLLVV DKETDNMYRL AHFSPFLYYQ SQELPNGSVK EAPAPTPTSL
EVSSPPDTTE EVDHKPKLCR LAKGENGYGF HLNAIRGLPG SFIKEVQKGG PADLAGLEDE
DVIIEVNGVN VLDEPYEKVV DRIQSSGKNV TLLVCGKKAY DYFQAKKIPI VSSLADPPDT
PPDSKEGIVV ESKHDSHMAK ERAHSTASHS SSNSEDTEM
