SCNNA_PANTR
ID SCNNA_PANTR Reviewed; 692 AA.
AC H2Q5A1;
DT 01-APR-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 2.
DT 03-AUG-2022, entry version 51.
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 Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16136131; DOI=10.1038/nature04072;
RG Chimpanzee sequencing and analysis consortium;
RT "Initial sequence of the chimpanzee genome and comparison with the human
RT genome.";
RL Nature 437:69-87(2005).
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; AACZ03089625; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AACZ03089626; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AACZ03089627; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AACZ03089628; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AACZ03089629; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AACZ03089630; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; H2Q5A1; -.
DR SMR; H2Q5A1; -.
DR STRING; 9598.ENSPTRP00000007816; -.
DR PaxDb; H2Q5A1; -.
DR Ensembl; ENSPTRT00000097030; ENSPTRP00000064198; ENSPTRG00000004571.
DR VGNC; VGNC:13442; SCNN1A.
DR eggNOG; KOG4294; Eukaryota.
DR GeneTree; ENSGT00940000160952; -.
DR InParanoid; H2Q5A1; -.
DR OMA; EKTRQCK; -.
DR Proteomes; UP000002277; Chromosome 12.
DR Bgee; ENSPTRG00000004571; Expressed in cortex of kidney and 13 other 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; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0034706; C:sodium channel complex; IBA:GO_Central.
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:0036254; P:cellular response to amiloride; IEA:Ensembl.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; IEA:Ensembl.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; IEA:Ensembl.
DR GO; GO:0050909; P:sensory perception of taste; IEA:UniProtKB-KW.
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 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 3: Inferred from homology;
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..692
FT /note="Amiloride-sensitive sodium channel subunit alpha"
FT /id="PRO_0000432714"
FT TOPO_DOM 1..108
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT TRANSMEM 109..129
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 130..585
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT TRANSMEM 586..606
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 607..692
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT REGION 1..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 627..692
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 628..655
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 656..671
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 692 AA; 78073 MW; 7AF35B9A527FB9D4 CRC64;
MSSIKGNKLE EQGPRPLQPT PGLMEGNKLE EQDSSPPQST PGLMKGDKRE EQGLGPEPAA
PQQPTAEEEA LIEFHRSYRE LFEFFCNNTT IHGAIRLVCS QHNRMKTAFW AVLWLCTFGM
MYWQFGLLFG EYFSYPVSLN INLNSDKLVF PAVTICTLNP YRYPEIKEEL EELDRITEQT
LFDLYKYSSF TTLVAGSRSR RDLRGTLPHP LQRLRVPPPP HGARRARSVA SSVRDNNPQV
DWKDWKIGFQ LCNQNKSDCF YQTYSSGVDA VREWYRFHYI NILSRLPETL PSLEKDTLGN
FIFACRFNQV SCNQANYSHF HHPMYGNCYT FNDKNNSNLW MSSMPGINNG LSLMLRAEQN
DFIPLLSTVT GARVMVHGQD EPAFMDDGGF NLRPGVETSI SMRKETLDRL GGDYGDCTKN
GSDVPVENLY PSKYTQQVCI HSCFQESMIK ECGCAYIFYP RPQNVEYCDY RKHSSWGYCY
YKLQVDFSSD HLGCFTKCRK PCSVTSYQLS AGYSRWPSVT SQEWVFQMLS RQNNYTVNNK
RNGVAKVNIF FKELNYKTNS ESPSVTMVTL LSNLGSQWSL WFGSSVLSVV EMAELIFDLL
VITFLMLLRR FRSRYWSPGR GGRGAQEVAS TLASSPPSHF CPHPTSLSLS QPGPAPSPAL
TAPPPAYATL GPRPSPGGST GAGSSACPLG GP