SCNNA_CAVPO
ID SCNNA_CAVPO Reviewed; 682 AA.
AC Q9R1N2; Q9QXF9;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 108.
DE RecName: Full=Amiloride-sensitive sodium channel subunit alpha;
DE AltName: Full=Alpha-NaCH;
DE AltName: Full=Epithelial Na(+) channel subunit alpha;
DE Short=Alpha-ENaC;
DE AltName: Full=Nonvoltage-gated sodium channel 1 subunit alpha;
DE AltName: Full=SCNEA;
GN Name=SCNN1A; Synonyms=ENAC;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RA Baines D.L., Bingle C.D., Vijayaragavan K., Olver R.E.;
RT "Domestic guinea pig lung alpha subunit of epithelial amiloride-sensitive
RT sodium channel (ENaC) mRNA.";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 27-682.
RC TISSUE=Colon mucosa;
RX PubMed=10764218; DOI=10.1007/s004249900213;
RA Schnizler M., Mastroberardino L., Reifarth F., Weber W.-M., Verrey F.,
RA Clauss W.;
RT "cAMP sensitivity conferred to the epithelial Na+ channel by alpha-subunit
RT cloned from guinea-pig colon.";
RL Pflugers Arch. 439:579-587(2000).
RN [3]
RP DEVELOPMENTAL STAGE.
RC TISSUE=Lung;
RX PubMed=10618159; DOI=10.1111/j.1469-7793.2000.t01-2-00147.xm;
RA Baines D.L., Folkesson H.G., Norlin A., Bingle C.D., Yuan H.T., Olver R.E.;
RT "The influence of mode of delivery, hormonal status and postnatal O2
RT environment on epithelial sodium channel (ENaC) expression in perinatal
RT guinea-pig lung.";
RL J. Physiol. (Lond.) 522:147-157(2000).
CC -!- FUNCTION: Sodium permeable non-voltage-sensitive ion channel inhibited
CC by the diuretic amiloride. Mediates the electrodiffusion of the luminal
CC sodium (and water, which follows osmotically) through the apical
CC membrane of epithelial cells. Plays an essential role in electrolyte
CC and blood pressure homeostasis, but also in airway surface liquid
CC homeostasis, which is important for proper clearance of mucus. Controls
CC the reabsorption of sodium in kidney, colon, lung and eccrine sweat
CC glands. Also plays a role in taste perception.
CC {ECO:0000250|UniProtKB:P37088}.
CC -!- ACTIVITY REGULATION: Activated by WNK1, WNK2, WNK3 and WNK4.
CC {ECO:0000250|UniProtKB:Q61180}.
CC -!- SUBUNIT: Heterotrimer containing an alpha/SCNN1A, a beta/SCNN1B and a
CC gamma/SCNN1G subunit. An additional delta/SCNN1D subunit exists only in
CC some organisms and can replace the alpha/SCNN1A subunit to form an
CC alternative channel with specific properties. Interacts with NEDD4 (via
CC WW domains). Interacts with NEDD4L (via WW domains). Interacts with
CC WWP1 (via WW domains). Interacts with WWP2 (via WW domains). Interacts
CC with the full-length immature form of PCSK9 (pro-PCSK9).
CC {ECO:0000250|UniProtKB:P37088}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:P37089}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P37089}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:P37088}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:P37088}. Cytoplasm
CC {ECO:0000250|UniProtKB:P37088}. Cytoplasmic vesicle, secretory vesicle,
CC acrosome {ECO:0000250|UniProtKB:P37089}. Cell projection, cilium,
CC flagellum {ECO:0000250|UniProtKB:P37089}. Note=In the oviduct and
CC bronchus, located on cilia in multi-ciliated cells. In endometrial non-
CC ciliated epithelial cells, restricted to apical surfaces. In epidermis,
CC located nearly uniformly in the cytoplasm in a granular distribution.
CC In sebaceous glands, observed only in the cytoplasmic space in between
CC the lipid vesicles. In eccrine sweat glands, mainly located at the
CC apical surface of the cells facing the lumen. In skin, in arrector pili
CC muscle cells and in adipocytes, located in the cytoplasm and
CC colocalized with actin fibers. {ECO:0000250|UniProtKB:P37088,
CC ECO:0000250|UniProtKB:P37089}.
CC -!- DEVELOPMENTAL STAGE: Expression in fetus is maximal at term and
CC declines postnatally. {ECO:0000269|PubMed:10618159}.
CC -!- PTM: Ubiquitinated; this targets individual subunits for endocytosis
CC and proteasome-mediated degradation. {ECO:0000250|UniProtKB:P37089}.
CC -!- PTM: ENaC cleavage by furin, and subsequently by prostasin (PRSS8),
CC leads to a stepwise increase in the open probability of the channel as
CC a result of release of the alpha and gamma subunit inhibitory tracts,
CC respectively. Interaction of ENaC subunit SCNN1B with BPIFA1 protects
CC ENaC against proteolytic activation. {ECO:0000250|UniProtKB:P37088}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P37089}.
CC -!- SIMILARITY: Belongs to the amiloride-sensitive sodium channel (TC
CC 1.A.6) family. SCNN1A subfamily. {ECO:0000305}.
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DR EMBL; AF071230; AAD50545.1; -; mRNA.
DR EMBL; AJ249296; CAB64910.1; -; mRNA.
DR AlphaFoldDB; Q9R1N2; -.
DR SMR; Q9R1N2; -.
DR STRING; 10141.ENSCPOP00000016986; -.
DR eggNOG; KOG4294; Eukaryota.
DR InParanoid; Q9R1N2; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0001669; C:acrosomal vesicle; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0060170; C:ciliary membrane; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0031514; C:motile cilium; ISS:UniProtKB.
DR GO; GO:0034706; C:sodium channel complex; ISS:UniProtKB.
DR GO; GO:0097228; C:sperm principal piece; ISS:UniProtKB.
DR GO; GO:0015280; F:ligand-gated sodium channel activity; IEA:InterPro.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; ISS:UniProtKB.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0050909; P:sensory perception of taste; IEA:UniProtKB-KW.
DR GO; GO:0055078; P:sodium ion homeostasis; ISS:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Cell membrane; Cell projection; Cilium; Cytoplasm; Cytoplasmic vesicle;
KW Flagellum; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Reference proteome; Sensory transduction; Sodium; Sodium channel;
KW Sodium transport; Taste; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation.
FT CHAIN 1..682
FT /note="Amiloride-sensitive sodium channel subunit alpha"
FT /id="PRO_0000181260"
FT TOPO_DOM 1..111
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT TRANSMEM 112..132
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 133..586
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT TRANSMEM 587..607
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 608..682
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT REGION 34..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 221..240
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 191
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 504
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 34
FT /note="A -> E (in Ref. 2; CAB64910)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="I -> T (in Ref. 2; CAB64910)"
FT /evidence="ECO:0000305"
FT CONFLICT 293..294
FT /note="RW -> SL (in Ref. 2; CAB64910)"
FT /evidence="ECO:0000305"
FT CONFLICT 298
FT /note="T -> A (in Ref. 2; CAB64910)"
FT /evidence="ECO:0000305"
FT CONFLICT 467
FT /note="E -> Q (in Ref. 2; CAB64910)"
FT /evidence="ECO:0000305"
FT CONFLICT 472..474
FT /note="TNH -> RKQ (in Ref. 2; CAB64910)"
FT /evidence="ECO:0000305"
FT CONFLICT 520..521
FT /note="AA -> VT (in Ref. 2; CAB64910)"
FT /evidence="ECO:0000305"
FT CONFLICT 547
FT /note="K -> N (in Ref. 2; CAB64910)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="T -> S (in Ref. 2; CAB64910)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 682 AA; 77071 MW; 40703EBDCAFE7C3C CRC64;
MLMRLLPLPS LTDGRPLGCC CTCQGSMKGD ELKAQGPLPP QPLQGPLKGD KCEQPGLGPE
PTAPQQHTEE EEALIEFHRS YRELFQFFCN NTTIHGAIRL VCSKHNRMKT AFWAVLWLCT
FGMMYWQFAL LFGEYFSYPV SLNINLNSDK LVFPAVTVCT LNPYRYKEIK EQLRELDRIT
QQTLFDLYNY NASSTLLAGA RSRRSLADTL PYPLQRIPVQ PEPRRARSSD PSSVRDNNPR
VDRRDWRVGF QLCNQNKSDC FYQTSSSGVD GVREWYRFHY INILAQVADT SPRWEEETLG
NFIFACRFNQ APCTQENYSH FHHPIYGNCY TFNNKNDSSL WMASMPGINN GLSLTLRTEQ
NDYIPLLSTV TGARVTVHGQ DEPAFMDDGG FNLRPGVETS ISMRKEALDR LGGSYGDCTQ
DGSDVPVQNL YPSKYTQQVC IHSCFQENMI KQCGCAYIFY PKPKGVEFCD YTNHSAWGYC
YYKLQGAFSS DSLGCFNKCR KPCNVTIYKL SAGYSRWPSA ASQDWIFQML SLQNNYTISN
KRNGVAKLNI YFKELNYRTN SESPSVTMVT LLSNLGSQWS LWFGSSVLSV VEMAEFMFDL
LVITLLMLLR RFRSRYWSPG RGARAAREVA CTPPPSLPSR FCAHSAFPTL TAPPPAYATL
SACPPLQGLA GASSAACAPR EP
