ID SCNNA_BOVIN Reviewed; 650 AA.
AC P55270; O02851;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 27-MAR-2024, entry version 143.
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;
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 [MRNA].
RC TISSUE=Kidney;
RX PubMed=7573394; DOI=10.1152/ajpcell.1995.269.3.c641;
RA Fuller C.M., Awayda M.S., Arrate M.P., Bradford A.L., Morris R.G.,
RA Canessa C.M., Rossier B.C., Benos D.J.;
RT "Cloning of a bovine renal epithelial Na+ channel subunit.";
RL Am. J. Physiol. 269:C641-C654(1995).
RN [2]
RP SEQUENCE REVISION TO C-TERMINUS.
RA Benos D.J.;
RL Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=22207244; DOI=10.1007/s00418-011-0904-1;
RA Enuka Y., Hanukoglu I., Edelheit O., Vaknine H., Hanukoglu A.;
RT "Epithelial sodium channels (ENaC) are uniformly distributed on motile
RT cilia in the oviduct and the respiratory airways.";
RL Histochem. Cell Biol. 137:339-353(2012).
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. In spermatogonia, spermatocytes and
CC round spermatids, located in the cytoplasm. Prior to spermiation,
CC location shifts from the cytoplasm to the spermatid tail. In
CC spermatozoa, localizes at the acrosome and the central region of the
CC sperm flagellum. {ECO:0000250|UniProtKB:P37088,
CC ECO:0000250|UniProtKB:P37089}.
CC -!- TISSUE SPECIFICITY: Expressed in kidney and lung (at protein level).
CC {ECO:0000269|PubMed:22207244}.
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; U14944; AAB48988.1; -; mRNA.
DR RefSeq; NP_777023.1; NM_174598.3.
DR AlphaFoldDB; P55270; -.
DR SMR; P55270; -.
DR STRING; 9913.ENSBTAP00000003413; -.
DR GlyCosmos; P55270; 1 site, No reported glycans.
DR PaxDb; 9913-ENSBTAP00000003413; -.
DR Ensembl; ENSBTAT00000003413.6; ENSBTAP00000003413.6; ENSBTAG00000002631.6.
DR GeneID; 282348; -.
DR KEGG; bta:282348; -.
DR CTD; 6337; -.
DR VEuPathDB; HostDB:ENSBTAG00000002631; -.
DR VGNC; VGNC:49961; SCNN1A.
DR eggNOG; KOG4294; Eukaryota.
DR GeneTree; ENSGT00940000160952; -.
DR InParanoid; P55270; -.
DR OMA; MRQCKQE; -.
DR OrthoDB; 5344287at2759; -.
DR Reactome; R-BTA-2672351; Stimuli-sensing channels.
DR Reactome; R-BTA-9730628; Sensory perception of salty taste.
DR Proteomes; UP000009136; Chromosome 5.
DR Bgee; ENSBTAG00000002631; Expressed in placenta and 91 other cell types or tissues.
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:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; IEA:Ensembl.
DR GO; GO:0031514; C:motile cilium; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; 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; IBA:GO_Central.
DR GO; GO:0050699; F:WW domain binding; IEA:Ensembl.
DR GO; GO:0071468; P:cellular response to acidic pH; IEA:Ensembl.
DR GO; GO:1904045; P:cellular response to aldosterone; IEA:Ensembl.
DR GO; GO:0006883; P:intracellular sodium ion homeostasis; IEA:Ensembl.
DR GO; GO:0050891; P:multicellular organismal-level water homeostasis; ISS:UniProtKB.
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:0098719; P:sodium ion import across plasma membrane; IEA:Ensembl.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISS:UniProtKB.
DR Gene3D; 2.60.470.10; Acid-sensing ion channels like domains; 1.
DR Gene3D; 1.10.287.770; YojJ-like; 1.
DR InterPro; IPR001873; ENaC.
DR InterPro; IPR004724; ENaC_chordates.
DR InterPro; IPR020903; ENaC_CS.
DR NCBIfam; TIGR00859; ENaC; 1.
DR PANTHER; PTHR11690:SF124; AMILORIDE-SENSITIVE SODIUM CHANNEL SUBUNIT ALPHA; 1.
DR PANTHER; PTHR11690; AMILORIDE-SENSITIVE SODIUM CHANNEL-RELATED; 1.
DR Pfam; PF00858; ASC; 1.
DR PRINTS; PR01078; AMINACHANNEL.
DR PROSITE; PS01206; ASC; 1.
PE 1: Evidence at protein 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..650
FT /note="Amiloride-sensitive sodium channel subunit alpha"
FT /id="PRO_0000181259"
FT TOPO_DOM 1..65
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT TRANSMEM 66..86
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 87..543
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT TRANSMEM 544..564
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 565..650
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 165..194
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 614..650
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 614..629
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 650 AA; 73793 MW; C17CBC61ECB60B9A CRC64;
MKGDKPEEPG PGPEPSGPPP PTEEEEALLE FHRSYRELFE FFCNNTTIHG AIRLVCSQHN
RMKTVFWAVL WLCTFGMMYW QFGQLFGEYF SYPVSLNINL NSDKLVFPAV SICTLNPYRY
KEIQEELEEL DRITEQTLFD LYKYNSSKTL VAHARSRRDL REPLPHPLQR LPVPAPPHAA
RGVRRAGSSM RDNNPQVNRK DWKIGFQLCN QNKSDCFYQT YSSGVDAVRE WYRFHYINIL
SRRRQDTSPS LEEDVLGKFI FTCRFNQDSC NEANYSHFHH PMYGNCYTFN DKNSSNLWMS
SMPGVNNGLS LTLRTEQNDF IPLLSTVTGA RVMVHERDEP AFMDDAGFNL RPGVETSISM
SKEAVDRLGG DYGDCTKNGS EVPVENLYNT KYTQQVCIHS CFQESMIKEC GCAYIFYPRP
DGVEFCDYRK HNSWGYCYYK LQDAFSSDRL GCFTKCRKPC SVTIYKLSAS YSQWPSATSQ
DWVFQMLSRQ NNYTIKNKRD GVAKLNIFFK ELNYKSNSES PSVTMVTLLS NLGSQWSLWF
GSSVLSVVEM AELIIDLLVI TFLMLLRRFR SRYWSPGRGG KGTQEVASTP AASLPSSFCP
HPAFFSSSPP DPAISPALSA PPPAYATLGP HPAPSGLAEA STSAHAPGEP
//
