SCNNA_RABIT
ID SCNNA_RABIT Reviewed; 640 AA.
AC O97741; Q9N133;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 25-MAY-2022, entry version 109.
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 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].
RA Kudlacek O., Weisz E., Wiener H., Plass H.;
RT "The rabbit epithelial sodium channel.";
RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 81-435.
RA Velazquez H., Silva T.C., Andujar E., Jaffer A., Ortiz D.;
RT "The rabbit DCT does not express amiloride sensitive sodium channel.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
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 -!- 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; AJ132108; CAA10571.1; -; mRNA.
DR EMBL; AF229025; AAF43680.1; -; mRNA.
DR RefSeq; NP_001076197.1; NM_001082728.1.
DR AlphaFoldDB; O97741; -.
DR SMR; O97741; -.
DR STRING; 9986.ENSOCUP00000016759; -.
DR GeneID; 100009488; -.
DR KEGG; ocu:100009488; -.
DR CTD; 6337; -.
DR eggNOG; KOG4294; Eukaryota.
DR InParanoid; O97741; -.
DR OrthoDB; 686369at2759; -.
DR Proteomes; UP000001811; Unplaced.
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..640
FT /note="Amiloride-sensitive sodium channel subunit alpha"
FT /id="PRO_0000181263"
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..539
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT TRANSMEM 540..560
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 561..640
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 595..617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 597..617
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 222
FT /note="S -> P (in Ref. 2; AAF43680)"
FT /evidence="ECO:0000305"
FT CONFLICT 264..265
FT /note="AF -> TS (in Ref. 2; AAF43680)"
FT /evidence="ECO:0000305"
FT CONFLICT 372..373
FT /note="TQ -> AE (in Ref. 2; AAF43680)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 640 AA; 72734 MW; 17C84C100F69E133 CRC64;
MKGDKREEQG PGPETVAPQQ PTEDEEALIE FHRSYRELFQ FFCNNTTIHG AIRLVCSKHN
RMKTAFWAVL WLCTFGMMYW QFGLLFGEYF SYPVNLNINL NSDKLVFPAV TVCTLNPYRY
PEITEQLKEL DSITQQTLLD LFKYNASTLE AQPRHRRDVH PPLPHPLQRL RVPPPRLEAR
RARSSASSVR DNSPEVGRKD WMIGFQLCNQ NRSDCFYQRY SSGVDAVREW YRFHYINILS
RLSDTSLSRE QLGNFIFTCR FNQAFCGDGN YSHFHHPMYG NCYTFNDKNN SSLWMSSMPG
INNGLSLTLR TEQNDFIPLL STVTGARVMV HGQDEPAFMD DGGFNLRPGV ETSISMRKES
LDRLGGDYGD CTQNGSDVPV KNLYRSKYTQ QVCIHSCFQE NMVKECGCAY IFYPLPEGVE
YCDYRKHNSW GYCYYKLQDA FSSDRLGCFT KCRKPCSVTN YELSAGYSRW PSVTSQDWVF
QMLSLQNNYT VSNKRNGVAK LNIYFKELNY KANSESPSVT MVTLLSNLGS QWSLWFGSSV
LSVVEMAELL FDLSVITFLM LLRRFRSRYW SPGRGAGGAR EVASSPVSAL PSRFCPHPTS
PSVPQPGPTL PPSLTAPPPA YATLGPCLSQ SGSACAPGEP
