SCNNG_RAT
ID SCNNG_RAT Reviewed; 650 AA.
AC P37091;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 25-MAY-2022, entry version 151.
DE RecName: Full=Amiloride-sensitive sodium channel subunit gamma;
DE AltName: Full=Epithelial Na(+) channel subunit gamma;
DE Short=Gamma-ENaC;
DE AltName: Full=Gamma-NaCH;
DE AltName: Full=Nonvoltage-gated sodium channel 1 subunit gamma;
DE AltName: Full=SCNEG;
GN Name=Scnn1g;
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], FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=Wistar; TISSUE=Distal colon;
RX PubMed=8188647; DOI=10.1016/s0021-9258(17)36706-6;
RA Lingueglia R., Renard S., Waldmann R., Voilley N., Champigny G., Plass H.,
RA Lazdunski M., Barbry P.;
RT "Different homologous subunits of the amiloride-sensitive Na+ channel are
RT differently regulated by aldosterone.";
RL J. Biol. Chem. 269:13736-13739(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Distal colon, and 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 [4]
RP FUNCTION, INTERACTION WITH SCNN1A AND SCNN1B, AND SUBCELLULAR LOCATION.
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 [5]
RP MUTAGENESIS OF LYS-6 AND LYS-13, AND UBIQUITINATION.
RX PubMed=9351815; DOI=10.1093/emboj/16.21.6325;
RA Staub O., Gautschi I., Ishikawa T., Breitschopf K., Ciechanover A.,
RA Schild L., Rotin D.;
RT "Regulation of stability and function of the epithelial Na+ channel (ENaC)
RT by ubiquitination.";
RL EMBO J. 16:6325-6336(1997).
RN [6]
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 [7]
RP INTERACTION 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, PubMed:8188647). Mediates
CC the electrodiffusion of the luminal sodium (and water, which follows
CC osmotically) through the apical membrane of epithelial cells
CC (PubMed:9118951, PubMed:8188647). Plays an essential role in
CC electrolyte and blood pressure homeostasis, but also in airway surface
CC liquid homeostasis, which is important for proper clearance of mucus
CC (By similarity). Controls the reabsorption of sodium in kidney, colon,
CC lung and sweat glands. Also plays a role in taste perception (By
CC similarity). {ECO:0000250|UniProtKB:P51170, ECO:0000269|PubMed:8188647,
CC ECO:0000269|PubMed:9118951}.
CC -!- ACTIVITY REGULATION: Activated by WNK1, WNK2, WNK3 and WNK4.
CC {ECO:0000250|UniProtKB:Q9WU39}.
CC -!- SUBUNIT: Heterotrimer containing an alpha/SCNN1A, a beta/SCNN1B and a
CC gamma/SCNN1G subunit (PubMed:8188647, PubMed:9118951). An additional
CC delta/SCNN1D subunit exists only in some organisms and can replace the
CC alpha/SCNN1A subunit to form an alternative channel with specific
CC properties (Probable). Interacts with NEDD4; via the WW domains
CC (PubMed:11323714). Interacts with NEDD4L; via the WW domains. Interacts
CC with WWP1; via the WW domains. Interacts with WWP2; via the WW domains.
CC Interacts with the full-length immature form of PCSK9 (pro-PCSK9) (By
CC similarity). {ECO:0000250|UniProtKB:P51170,
CC ECO:0000269|PubMed:11323714, ECO:0000269|PubMed:9118951,
CC ECO:0000305|PubMed:8188647}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000269|PubMed:8188647,
CC ECO:0000269|PubMed:9118951}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P37089}. Note=Apical membrane of epithelial
CC cells. {ECO:0000269|PubMed:8188647}.
CC -!- PTM: Phosphorylated on serine and threonine residues. Aldosterone and
CC insulin increase the basal level of phosphorylation.
CC {ECO:0000269|PubMed:9501257}.
CC -!- PTM: Ubiquitinated; this targets individual subunits for endocytosis
CC and proteasome-mediated degradation. {ECO:0000269|PubMed:9351815}.
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:P51170}.
CC -!- SIMILARITY: Belongs to the amiloride-sensitive sodium channel (TC
CC 1.A.6) family. SCNN1G subfamily. {ECO:0000305}.
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DR EMBL; X77933; CAA54905.1; -; mRNA.
DR EMBL; X78034; CAA54964.1; -; mRNA.
DR EMBL; U37539; AAB58459.1; -; mRNA.
DR EMBL; U37540; AAB58460.1; -; mRNA.
DR PIR; A54065; A54065.
DR RefSeq; NP_058742.1; NM_017046.1.
DR AlphaFoldDB; P37091; -.
DR SMR; P37091; -.
DR BioGRID; 246892; 8.
DR ComplexPortal; CPX-314; Amiloride-sensitive sodium channel complex, alpha-beta-gamma.
DR DIP; DIP-61327N; -.
DR ELM; P37091; -.
DR IntAct; P37091; 3.
DR STRING; 10116.ENSRNOP00000024057; -.
DR GlyGen; P37091; 3 sites.
DR iPTMnet; P37091; -.
DR PhosphoSitePlus; P37091; -.
DR PaxDb; P37091; -.
DR GeneID; 24768; -.
DR KEGG; rno:24768; -.
DR UCSC; RGD:3641; rat.
DR CTD; 6340; -.
DR RGD; 3641; Scnn1g.
DR eggNOG; KOG4294; Eukaryota.
DR InParanoid; P37091; -.
DR OrthoDB; 686369at2759; -.
DR PhylomeDB; P37091; -.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR Reactome; R-RNO-9730628; Sensory perception of salty taste.
DR PRO; PR:P37091; -.
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: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:0005216; F:ion channel activity; ISO:RGD.
DR GO; GO:0015280; F:ligand-gated sodium channel activity; IDA:RGD.
DR GO; GO:0050699; F:WW domain binding; IPI: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:0050891; P:multicellular organismal water homeostasis; ISS:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; IC:ComplexPortal.
DR GO; GO:0001666; P:response to hypoxia; IEP: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: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 Cell membrane; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Sensory transduction; Sodium;
KW Sodium channel; Sodium transport; Taste; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..650
FT /note="Amiloride-sensitive sodium channel subunit gamma"
FT /id="PRO_0000181279"
FT TOPO_DOM 1..55
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT TRANSMEM 56..76
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 77..542
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT TRANSMEM 543..563
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 564..650
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P37089"
FT REGION 577..628
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 578..594
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 498
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 6
FT /note="K->R: Interferes with ubiquitination and increases
FT amiloride-sensitive current and the number of active
FT channels; when associated with R-13."
FT /evidence="ECO:0000269|PubMed:9351815"
FT MUTAGEN 13
FT /note="K->R: Interferes with ubiquitination and increases
FT amiloride-sensitive current and the number of active
FT channels; when associated with R-6."
FT /evidence="ECO:0000269|PubMed:9351815"
FT CONFLICT 53
FT /note="R -> P (in Ref. 1; CAA54905)"
FT /evidence="ECO:0000305"
FT CONFLICT 573
FT /note="W -> C (in Ref. 1; CAA54905)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 650 AA; 74066 MW; 701F9B28B3250D8F CRC64;
MAPGEKIKAK IKKNLPVRGP QAPTIKDLMH WYCMNTNTHG CRRIVVSRGR LRRLLWIAFT
LTAVALIIWQ CALLVFSFYT VSVSIKVHFQ KLDFPAVTIC NINPYKYSAV SDLLTDLDSE
TKQALLSLYG VKESRKRREA GSMPSTLEGT PPRFFKLIPL LVFNENEKGK ARDFFTGRKR
KISGKIIHKA SNVMHVHESK KLVGFQLCSN DTSDCATYTF SSGINAIQEW YKLHYMNIMA
QVPLEKKINM SYSAEELLVT CFFDGMSCDA RNFTLFHHPM YGNCYTFNNK ENATILSTSM
GGSEYGLQVI LYINEDEYNP FLVSSTGAKV LIHQQNEYPF IEDVGMEIET AMSTSIGMHL
TESFKLSEPY SQCTEDGSDV PVTNIYNAAY SLQICLYSCF QTKMVEKCGC AQYSQPLPPA
ANYCNYQQHP NWMYCYYQLY QAFVREELGC QSVCKQSCSF KEWTLTTSLA QWPSEASEKW
LLNVLTWDQS QQINKKLNKT DLAKLLIFYK DLNQRSIMES PANSIEMLLS NFGGQLGLWM
SCSVVCVIEI IEVFFIDFFS IIARRQWHKA KDWWARRQTP PSTETPSSRQ GQDNPALDTD
DDLPTFTSAM RLPPAPGSTV PGTPPPRYNT LRLDRAFSSQ LTDTQLTNEL
