ID   SCNNG_MOUSE             Reviewed;         655 AA.
AC   Q9WU39;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   24-JAN-2024, entry version 167.
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   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND
RP   TISSUE SPECIFICITY.
RC   STRAIN=C57BL/6J; TISSUE=Kidney;
RX   PubMed=10409305; DOI=10.1152/ajprenal.1999.277.1.f121;
RA   Ahn Y.J., Brooker D.R., Kosari F., Harte B.J., Li J., Mackler S.A.,
RA   Kleyman T.R.;
RT   "Cloning and functional expression of the mouse epithelial sodium
RT   channel.";
RL   Am. J. Physiol. 277:F121-F129(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Kidney;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   INTERACTION WITH NEDD4 AND NEDD4L.
RX   PubMed=11244092; DOI=10.1074/jbc.c000906200;
RA   Harvey K.F., Dinudom A., Cook D.I., Kumar S.;
RT   "The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial
RT   sodium channel.";
RL   J. Biol. Chem. 276:8597-8601(2001).
RN   [4]
RP   INTERACTION WITH NEDD4L.
RX   PubMed=12424229; DOI=10.1096/fj.02-0497fje;
RA   Fotia A.B., Dinudom A., Shearwin K.E., Koch J.-P., Korbmacher C.,
RA   Cook D.I., Kumar S.;
RT   "The role of individual Nedd4-2 (KIAA0439) WW domains in binding and
RT   regulating epithelial sodium channels.";
RL   FASEB J. 17:70-72(2003).
RN   [5]
RP   INTERACTION WITH NEDD4 AND NEDD4L.
RX   PubMed=15123669; DOI=10.1074/jbc.m402820200;
RA   Fotia A.B., Ekberg J., Adams D.J., Cook D.I., Poronnik P., Kumar S.;
RT   "Regulation of neuronal voltage-gated sodium channels by the ubiquitin-
RT   protein ligases Nedd4 and Nedd4-2.";
RL   J. Biol. Chem. 279:28930-28935(2004).
RN   [6]
RP   ACTIVITY REGULATION.
RX   PubMed=20525693; DOI=10.1074/jbc.m110.103432;
RA   Heise C.J., Xu B.E., Deaton S.L., Cha S.K., Cheng C.J., Earnest S.,
RA   Sengupta S., Juang Y.C., Stippec S., Xu Y., Zhao Y., Huang C.L., Cobb M.H.;
RT   "Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium
RT   channel are regulated by multiple with no lysine (WNK) family members.";
RL   J. Biol. Chem. 285:25161-25167(2010).
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 sweat glands.
CC       Also plays a role in taste perception. {ECO:0000250|UniProtKB:P51170,
CC       ECO:0000269|PubMed:10409305}.
CC   -!- ACTIVITY REGULATION: Activated by WNK1, WNK2, WNK3 and WNK4.
CC       {ECO:0000269|PubMed:20525693}.
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 (Probable). Interacts with
CC       NEDD4; via the WW domains (PubMed:11244092, PubMed:15123669). Interacts
CC       with NEDD4L; via the WW domains (PubMed:12424229, PubMed:11244092,
CC       PubMed:15123669). Interacts with WWP1; via the WW domains (By
CC       similarity). Interacts with WWP2; via the WW domains. Interacts with
CC       the full-length immature form of PCSK9 (pro-PCSK9) (By similarity).
CC       {ECO:0000250|UniProtKB:P51170, ECO:0000269|PubMed:11244092,
CC       ECO:0000269|PubMed:12424229, ECO:0000269|PubMed:15123669,
CC       ECO:0000305|PubMed:10409305}.
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000303|PubMed:10409305}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:P37089}. Note=Apical membrane of epithelial
CC       cells. {ECO:0000303|PubMed:10409305}.
CC   -!- TISSUE SPECIFICITY: Lung and kidney. {ECO:0000269|PubMed:10409305}.
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   -!- PTM: Phosphorylated on serine and threonine residues. Aldosterone and
CC       insulin increase the basal level of phosphorylation.
CC       {ECO:0000250|UniProtKB:P37091}.
CC   -!- PTM: Ubiquitinated; this targets individual subunits for endocytosis
CC       and proteasome-mediated degradation. {ECO:0000250|UniProtKB:P37091}.
CC   -!- SIMILARITY: Belongs to the amiloride-sensitive sodium channel
CC       (TC 1.A.6) family. SCNN1G subfamily. {ECO:0000305}.
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DR   EMBL; AF112187; AAD21246.1; -; mRNA.
DR   EMBL; BC021338; AAH21338.1; -; mRNA.
DR   CCDS; CCDS21803.1; -.
DR   RefSeq; NP_035456.1; NM_011326.3.
DR   AlphaFoldDB; Q9WU39; -.
DR   SMR; Q9WU39; -.
DR   BioGRID; 203107; 7.
DR   ComplexPortal; CPX-315; Amiloride-sensitive sodium channel complex, alpha-beta-gamma.
DR   STRING; 10090.ENSMUSP00000000221; -.
DR   GuidetoPHARMACOLOGY; 741; -.
DR   GlyCosmos; Q9WU39; 3 sites, No reported glycans.
DR   GlyGen; Q9WU39; 3 sites.
DR   iPTMnet; Q9WU39; -.
DR   PhosphoSitePlus; Q9WU39; -.
DR   SwissPalm; Q9WU39; -.
DR   MaxQB; Q9WU39; -.
DR   PaxDb; 10090-ENSMUSP00000000221; -.
DR   ProteomicsDB; 253424; -.
DR   Antibodypedia; 25924; 437 antibodies from 33 providers.
DR   DNASU; 20278; -.
DR   Ensembl; ENSMUST00000000221.6; ENSMUSP00000000221.6; ENSMUSG00000000216.9.
DR   GeneID; 20278; -.
DR   KEGG; mmu:20278; -.
DR   UCSC; uc009jnv.1; mouse.
DR   AGR; MGI:104695; -.
DR   CTD; 6340; -.
DR   MGI; MGI:104695; Scnn1g.
DR   VEuPathDB; HostDB:ENSMUSG00000000216; -.
DR   eggNOG; KOG4294; Eukaryota.
DR   GeneTree; ENSGT00940000160352; -.
DR   HOGENOM; CLU_020415_0_0_1; -.
DR   InParanoid; Q9WU39; -.
DR   OMA; SCDSRNF; -.
DR   OrthoDB; 5344287at2759; -.
DR   PhylomeDB; Q9WU39; -.
DR   TreeFam; TF330663; -.
DR   Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR   Reactome; R-MMU-9730628; Sensory perception of salty taste.
DR   BioGRID-ORCS; 20278; 0 hits in 78 CRISPR screens.
DR   PRO; PR:Q9WU39; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; Q9WU39; Protein.
DR   Bgee; ENSMUSG00000000216; Expressed in right lung lobe and 45 other cell types or tissues.
DR   GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR   GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR   GO; GO:0016020; C:membrane; IDA:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0034706; C:sodium channel complex; IDA:MGI.
DR   GO; GO:0015280; F:ligand-gated sodium channel activity; IDA:MGI.
DR   GO; GO:0005216; F:monoatomic ion channel activity; ISO:MGI.
DR   GO; GO:0050699; F:WW domain binding; IPI:MGI.
DR   GO; GO:0071468; P:cellular response to acidic pH; ISO:MGI.
DR   GO; GO:1904045; P:cellular response to aldosterone; IDA:MGI.
DR   GO; GO:1904117; P:cellular response to vasopressin; NAS:ComplexPortal.
DR   GO; GO:0006883; P:intracellular sodium ion homeostasis; IDA:ComplexPortal.
DR   GO; GO:0050891; P:multicellular organismal-level water homeostasis; ISS:UniProtKB.
DR   GO; GO:0008217; P:regulation of blood pressure; NAS:ComplexPortal.
DR   GO; GO:0050914; P:sensory perception of salty taste; NAS:ComplexPortal.
DR   GO; GO:0050915; P:sensory perception of sour taste; NAS: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:MGI.
DR   GO; GO:0006814; P:sodium ion transport; IDA:MGI.
DR   GO; GO:0035313; P:wound healing, spreading of epidermal cells; ISO:MGI.
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:SF19; AMILORIDE-SENSITIVE SODIUM CHANNEL SUBUNIT GAMMA; 1.
DR   PANTHER; PTHR11690; AMILORIDE-SENSITIVE SODIUM CHANNEL-RELATED; 1.
DR   Pfam; PF00858; ASC; 1.
DR   PRINTS; PR01078; AMINACHANNEL.
DR   PROSITE; PS01206; ASC; 1.
DR   Genevisible; Q9WU39; MM.
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..655
FT                   /note="Amiloride-sensitive sodium channel subunit gamma"
FT                   /id="PRO_0000181277"
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..547
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:P37089"
FT   TRANSMEM        548..568
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        569..655
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:P37089"
FT   REGION          582..636
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        585..601
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        215
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        277
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        503
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   655 AA;  74635 MW;  ABADDA9D6160596D CRC64;
     MAPGEKIKAK IKKNLPVRGP QAPTIKDLMH WYCLNTNTHG CRRIVVSRGR LRRLLWIAFT
     LTAVALIIWQ CALLVFSFYT VSVSIKVHFQ KLDFPAVTIC NINPYKYSAV SDLLTDLDSE
     TKQALLSLYG VKDVLDSTPR KRREAGSMRS TWEGTPPRFL NLIPLLVFNE NEKGKARDFF
     TGRKRKISGK IIHKASNVMH VHESKKLVGF QLCSNDTSDC ATYTFSSGIN AIQEWYKLHY
     MNIMAQVPLE KKINMSYSAE ELLVTCFFDG MSCDARNFTL FHHPMYGNCY TFNNRENATI
     LSTSMGGSEY GLQVILYINE DEYNPFLVSS TGAKVLVHQQ NEYPFIEDVG TEIETAMSTS
     IGMHLTESFK LSEPYSQCTE DGSDVPVTNI YNAAYSLQIC LYSCFQTKMV EKCGCAQYSQ
     PLPPAANYCN YQQHPNWMYC YYQLYQAFVR EELGCQSVCK QSCSFKEWTL TTSLAQWPSE
     ASEKWLLNVL TWDQSQQINK KLNKTDLAKL LIFYKDLNQR SIMESPANSI EMLLSNFGGQ
     LGLWMSCSVV CVIEIIEVFF IDFFSIIARR QWQKAKDWWA RRRTPPSTET PSSQQGQDNP
     ALDTDDDLPT FTSAMRLPPA PEAPVPGTPP PRYNTLRLDS AFSSQLTDTQ LTNEF
//