SCNNB_RAT
ID SCNNB_RAT Reviewed; 638 AA.
AC P37090; O09183;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 25-MAY-2022, entry version 152.
DE RecName: Full=Amiloride-sensitive sodium channel subunit beta;
DE AltName: Full=Beta-NaCH;
DE AltName: Full=Epithelial Na(+) channel subunit beta;
DE Short=Beta-ENaC;
DE AltName: Full=Nonvoltage-gated sodium channel 1 subunit beta;
DE AltName: Full=SCNEB;
GN Name=Scnn1b;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Distal colon epithelium;
RX PubMed=8107805; DOI=10.1038/367463a0;
RA Canessa C.M., Schild L., Buell G., Thorens B., Gautschi I.,
RA Horisberger J.-D., Rossier B.C.;
RT "Amiloride-sensitive epithelial Na+ channel is made of three homologous
RT subunits.";
RL Nature 367:463-467(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=9039092; DOI=10.1161/01.hyp.29.1.131;
RA Kreutz R., Struk B., Rubattu S., Hubner N., Szpirer J., Szpirer C.,
RA Ganten D., Lindpaintner K.;
RT "Role of the alpha-, beta-, and gamma-subunits of epithelial sodium channel
RT in a model of polygenic hypertension.";
RL Hypertension 29:131-136(1997).
RN [3]
RP FUNCTION, INTERACTION WITH SCNN1A AND SCNN1G, SUBCELLULAR LOCATION, AND
RP TOPOLOGY.
RX PubMed=9118951; DOI=10.1093/emboj/16.5.899;
RA Gruender S., Firsov D., Chang S.S., Jaeger N.F., Gautschi I., Schild L.,
RA Lifton R.P., Rossier B.C.;
RT "A mutation causing pseudohypoaldosteronism type 1 identifies a conserved
RT glycine that is involved in the gating of the epithelial sodium channel.";
RL EMBO J. 16:899-907(1997).
RN [4]
RP PHOSPHORYLATION.
RX PubMed=9501257; DOI=10.1073/pnas.95.6.3301;
RA Shimkets R.A., Lifton R., Canessa C.M.;
RT "In vivo phosphorylation of the epithelial sodium channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:3301-3305(1998).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=11352848; DOI=10.1152/ajprenal.2001.280.6.f1093;
RA Hager H., Kwon T.H., Vinnikova A.K., Masilamani S., Brooks H.L.,
RA Frokiaer J., Knepper M.A., Nielsen S.;
RT "Immunocytochemical and immunoelectron microscopic localization of alpha-,
RT beta-, and gamma-ENaC in rat kidney.";
RL Am. J. Physiol. 280:F1093-F1106(2001).
RN [6]
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=11773057; DOI=10.1074/jbc.m110904200;
RA Hanwell D., Ishikawa T., Saleki R., Rotin D.;
RT "Trafficking and cell surface stability of the epithelial Na+ channel
RT expressed in epithelial Madin-Darby canine kidney cells.";
RL J. Biol. Chem. 277:9772-9779(2002).
RN [7]
RP MUTAGENESIS OF PRO-616; TYR-618 AND LEU-621, AND INTERACTION WITH NEDD4.
RX PubMed=12654927; DOI=10.1074/jbc.m211153200;
RA Henry P.C., Kanelis V., O'Brien C.M., Kim B., Gautschi I., Forman-Kay J.D.,
RA Schild L., Rotin D.;
RT "Affinity and specificity of interactions between Nedd4 isoforms and
RT ENaC.";
RL J. Biol. Chem. 278:20019-20028(2003).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=30659401; DOI=10.1007/s10735-019-09813-3;
RA Sharma S., Hanukoglu I.;
RT "Mapping the sites of localization of epithelial sodium channel (ENaC) and
RT CFTR in segments of the mammalian epididymis.";
RL J. Mol. Histol. 50:141-154(2019).
RN [9]
RP STRUCTURE BY NMR OF 607-621 IN COMPLEX WITH NEDD4.
RX PubMed=11323714; DOI=10.1038/87562;
RA Kanelis V., Rotin D., Forman-Kay J.D.;
RT "Solution structure of a Nedd4 WW domain-ENaC peptide complex.";
RL Nat. Struct. Biol. 8:407-412(2001).
CC -!- FUNCTION: Sodium permeable non-voltage-sensitive ion channel inhibited
CC by the diuretic amiloride (PubMed:9118951). Mediates the
CC electrodiffusion of the luminal sodium (and water, which follows
CC osmotically) through the apical membrane of epithelial cells. Plays an
CC essential role in electrolyte and blood pressure homeostasis, but also
CC in airway surface liquid homeostasis, which is important for proper
CC clearance of mucus. Controls the reabsorption of sodium in kidney,
CC colon, lung and sweat glands. Also plays a role in taste perception.
CC {ECO:0000250|UniProtKB:P51168, ECO:0000269|PubMed:9118951}.
CC -!- ACTIVITY REGULATION: Activated by WNK1, WNK2, WNK3 and WNK4.
CC {ECO:0000250|UniProtKB:Q9WU38}.
CC -!- SUBUNIT: Heterotrimer containing an alpha/SCNN1A, a beta/SCNN1B and a
CC gamma/SCNN1G subunit (PubMed:9118951). An additional delta/SCNN1D
CC subunit exists only in some organisms and can replace the alpha/SCNN1A
CC subunit to form an alternative channel with specific properties (By
CC similarity). Interacts with NEDD4 (via WW domains) (PubMed:12654927,
CC PubMed:11323714). Interacts with NEDD4L (via WW domains) (By
CC similarity). Interacts with WWP1 (via WW domains) (By similarity).
CC Interacts with WWP2 (via WW domains) (By similarity). Interacts with
CC the full-length immature form of PCSK9 (pro-PCSK9) (By similarity).
CC Interacts (N-glycosylated) with BPIFA1; the interaction is direct and
CC inhibits the proteolytic processing of SCNN1A and SCNN1G and the
CC activation of ENaC (By similarity). {ECO:0000250|UniProtKB:P51168,
CC ECO:0000269|PubMed:11323714, ECO:0000269|PubMed:12654927,
CC ECO:0000269|PubMed:9118951}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:11352848, ECO:0000269|PubMed:11773057,
CC ECO:0000269|PubMed:9118951}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P37089}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:11352848, ECO:0000269|PubMed:11773057}. Note=Apical
CC membrane of epithelial cells. {ECO:0000269|PubMed:11352848,
CC ECO:0000269|PubMed:11773057}.
CC -!- TISSUE SPECIFICITY: Expressed in lung and epididymis (PubMed:30659401).
CC In the caput region of the epididymis, expressed at the luminal and
CC basolateral surfaces of the ducts and in the smooth muscle coat
CC (PubMed:30659401). In the caudal region of the epididymis, expressed
CC along the luminal border but not continuously, in the smooth muscle
CC coat, in the interstitial muscle tissue and in sperm in the caudal
CC lumen (PubMed:30659401). {ECO:0000269|PubMed:30659401}.
CC -!- PTM: N-glycosylated (PubMed:11773057). N-glycosylation is required for
CC interaction with BPIFA1 (By similarity). {ECO:0000250|UniProtKB:P51168,
CC ECO:0000269|PubMed:11773057}.
CC -!- PTM: Phosphorylated on serine and threonine residues. Aldosterone and
CC insulin increase the basal level of phosphorylation.
CC {ECO:0000269|PubMed:9501257}.
CC -!- SIMILARITY: Belongs to the amiloride-sensitive sodium channel (TC
CC 1.A.6) family. SCNN1B subfamily. {ECO:0000305}.
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DR EMBL; X77932; CAA54904.1; -; mRNA.
DR EMBL; U35174; AAB58457.1; -; mRNA.
DR EMBL; U35175; AAB58458.1; -; mRNA.
DR PIR; S41159; S41159.
DR RefSeq; NP_036780.1; NM_012648.1.
DR PDB; 1I5H; NMR; -; B=607-621.
DR PDBsum; 1I5H; -.
DR AlphaFoldDB; P37090; -.
DR SMR; P37090; -.
DR BioGRID; 246891; 2.
DR ComplexPortal; CPX-314; Amiloride-sensitive sodium channel complex, alpha-beta-gamma.
DR IntAct; P37090; 2.
DR STRING; 10116.ENSRNOP00000063755; -.
DR CarbonylDB; P37090; -.
DR GlyGen; P37090; 2 sites.
DR iPTMnet; P37090; -.
DR PhosphoSitePlus; P37090; -.
DR PaxDb; P37090; -.
DR GeneID; 24767; -.
DR KEGG; rno:24767; -.
DR UCSC; RGD:3640; rat.
DR CTD; 6338; -.
DR RGD; 3640; Scnn1b.
DR eggNOG; KOG4294; Eukaryota.
DR InParanoid; P37090; -.
DR OrthoDB; 686369at2759; -.
DR PhylomeDB; P37090; -.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR Reactome; R-RNO-9730628; Sensory perception of salty taste.
DR EvolutionaryTrace; P37090; -.
DR PRO; PR:P37090; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IC:ComplexPortal.
DR GO; GO:0034706; C:sodium channel complex; IPI:ComplexPortal.
DR GO; GO:0015280; F:ligand-gated sodium channel activity; IDA:RGD.
DR GO; GO:0050699; F:WW domain binding; IDA:RGD.
DR GO; GO:0032341; P:aldosterone metabolic process; ISO:RGD.
DR GO; GO:0014824; P:artery smooth muscle contraction; ISO:RGD.
DR GO; GO:0071468; P:cellular response to acidic pH; ISO:RGD.
DR GO; GO:1904045; P:cellular response to aldosterone; ISO:RGD.
DR GO; GO:0036254; P:cellular response to amiloride; IDA:ComplexPortal.
DR GO; GO:1904117; P:cellular response to vasopressin; IC:ComplexPortal.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IDA:ComplexPortal.
DR GO; GO:0042045; P:epithelial fluid transport; ISO:RGD.
DR GO; GO:0034101; P:erythrocyte homeostasis; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0002269; P:leukocyte activation involved in inflammatory response; ISO:RGD.
DR GO; GO:0070254; P:mucus secretion; ISO:RGD.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; ISS:UniProtKB.
DR GO; GO:0002283; P:neutrophil activation involved in immune response; ISO:RGD.
DR GO; GO:0070944; P:neutrophil-mediated killing of bacterium; ISO:RGD.
DR GO; GO:0055075; P:potassium ion homeostasis; ISO:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; IC:ComplexPortal.
DR GO; GO:0002028; P:regulation of sodium ion transport; IDA:RGD.
DR GO; GO:0032094; P:response to food; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0050914; P:sensory perception of salty taste; IC:ComplexPortal.
DR GO; GO:0050915; P:sensory perception of sour taste; IC:ComplexPortal.
DR GO; GO:0055078; P:sodium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; IDA:ComplexPortal.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:RGD.
DR GO; GO:0006814; P:sodium ion transport; IDA:RGD.
DR GO; GO:0097274; P:urea homeostasis; ISO:RGD.
DR GO; GO:0035313; P:wound healing, spreading of epidermal cells; IMP:RGD.
DR InterPro; IPR001873; ENaC.
DR InterPro; IPR004724; ENaC_chordates.
DR InterPro; IPR020903; ENaC_CS.
DR PANTHER; PTHR11690; PTHR11690; 1.
DR Pfam; PF00858; ASC; 1.
DR PRINTS; PR01078; AMINACHANNEL.
DR TIGRFAMs; TIGR00859; ENaC; 1.
DR PROSITE; PS01206; ASC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasmic vesicle; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Sensory transduction; Sodium; Sodium channel; Sodium transport; Taste;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..638
FT /note="Amiloride-sensitive sodium channel subunit beta"
FT /id="PRO_0000181271"
FT TOPO_DOM 1..50
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT TRANSMEM 51..71
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 72..530
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:9118951"
FT TRANSMEM 531..551
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 552..638
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT REGION 598..620
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 631
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WU38"
FT MOD_RES 633
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WU38"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 616
FT /note="P->A: Strong increase in channel activity."
FT /evidence="ECO:0000269|PubMed:12654927"
FT MUTAGEN 618
FT /note="Y->A: Strong increase in channel activity."
FT /evidence="ECO:0000269|PubMed:12654927"
FT MUTAGEN 621
FT /note="L->A: 2-fold increase in channel activity."
FT /evidence="ECO:0000269|PubMed:12654927"
FT CONFLICT 567
FT /note="A -> R (in Ref. 1; CAA54904)"
FT /evidence="ECO:0000305"
FT CONFLICT 586..587
FT /note="FG -> CV (in Ref. 1; CAA54904)"
FT /evidence="ECO:0000305"
FT TURN 618..620
FT /evidence="ECO:0007829|PDB:1I5H"
SQ SEQUENCE 638 AA; 71995 MW; 79176A282D5079F1 CRC64;
MPVKKYLLKC LHRLQKGPGY TYKELLVWYC NNTNTHGPKR IICEGPKKKA MWFLLTLLFA
CLVCWQWGVF IQTYLSWEVS VSLSMGFKTM NFPAVTVCNS SPFQYSKVKH LLKDLYKLME
AVLDKILAPK SSHTNTTSTL NFTIWNHTPL VLIDERNPDH PVVLNLFGDS HNSSNPAPGS
TCNAQGCKVA MRLCSANGTV CTFRNFTSAT QAVTEWYILQ ATNIFSQVLP QDLVGMGYAP
DRIILACLFG TEPCSHRNFT PIFYPDYGNC YIFNWGMTEK ALPSANPGTE FGLKLILDIG
QEDYVPFLAS TAGARLMLHE QRTYPFIREE GIYAMAGTET SIGVLLDKLQ GKGEPYSPCT
MNGSDVAIQN LYSDYNTTYS IQACLHSCFQ DHMIHNCSCG HYLYPLPAGE KYCNNRDFPD
WAYCYLSLQM SVVQRETCLS MCKESCNDTQ YKMTISMADW PSEASEDWIL HVLSQERDQS
SNITLSRKGI VKLNIYFQEF NYRTIEESPA NNIVWLLSNL GGQFGFWMGG SVLCLIEFGE
IIIDFIWITV IKLVASCKGL RRRRPQAPYT GPPPTVAELV EAHTNFGFQP DTTSCRPNAE
VYPDQQTLPI PGTPPPNYDS LRLQPLDTME SDSEVEAI
