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Protein

Amiloride-sensitive sodium channel subunit alpha

Gene

Scnn1a

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells (PubMed:8382172). Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception (By similarity).By similarity1 Publication

Enzyme regulationi

Activated by WNK1, WNK2, WNK3 and WNK4.By similarity

GO - Molecular functioni

  • actin binding Source: RGD
  • ligand-gated sodium channel activity Source: RGD
  • WW domain binding Source: RGD

GO - Biological processi

  • multicellular organismal water homeostasis Source: UniProtKB
  • regulation of blood pressure Source: RGD
  • regulation of body fluid levels Source: RGD
  • response to stimulus Source: UniProtKB-KW
  • sensory perception of taste Source: UniProtKB-KW
  • sodium ion homeostasis Source: UniProtKB
  • sodium ion transmembrane transport Source: UniProtKB
  • sodium ion transport Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel

Keywords - Biological processi

Ion transport, Sensory transduction, Sodium transport, Taste, Transport

Keywords - Ligandi

Sodium

Names & Taxonomyi

Protein namesi
Recommended name:
Amiloride-sensitive sodium channel subunit alpha
Alternative name(s):
Alpha-NaCH
Epithelial Na(+) channel subunit alpha
Short name:
Alpha-ENaC
Nonvoltage-gated sodium channel 1 subunit alpha
SCNEA
Gene namesi
Name:Scnn1a
Synonyms:Renac
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3639. Scnn1a.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 110Cytoplasmic2 PublicationsAdd BLAST110
Transmembranei111 – 131Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini132 – 589Extracellular2 PublicationsAdd BLAST458
Transmembranei590 – 610Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini611 – 698Cytoplasmic2 PublicationsAdd BLAST88

GO - Cellular componenti

  • apical plasma membrane Source: RGD
  • ciliary membrane Source: UniProtKB
  • cortical actin cytoskeleton Source: RGD
  • integral component of plasma membrane Source: UniProtKB
  • motile cilium Source: UniProtKB
  • sodium channel complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi588S → I: Changes function of the channel including conductance, gating, selectivity and voltage dependence. 1 Publication1
Mutagenesisi592S → T: Changes function of the channel including conductance, gating, selectivity and voltage dependence. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001812641 – 698Amiloride-sensitive sodium channel subunit alphaAdd BLAST698

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi190N-linked (GlcNAc...)1 Publication1
Glycosylationi259N-linked (GlcNAc...)1 Publication1
Glycosylationi320N-linked (GlcNAc...)1 Publication1
Glycosylationi339N-linked (GlcNAc...)1 Publication1
Glycosylationi424N-linked (GlcNAc...)1 Publication1
Glycosylationi538N-linked (GlcNAc...)1 Publication1

Post-translational modificationi

Ubiquitinated; this targets individual subunits for endocytosis and proteasome-mediated degradation.1 Publication
ENaC cleavage by furin, and subsequently by prostasin (PRSS8), leads to a stepwise increase in the open probability of the channel as a result of release of the alpha and gamma subunit inhibitory tracts, respectively. Interaction of ENaC subunit SCNN1B with BPIFA1 protects ENaC against proteolytic activation.By similarity
N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Ubl conjugation

Proteomic databases

PaxDbiP37089.
PRIDEiP37089.

PTM databases

iPTMnetiP37089.
PhosphoSitePlusiP37089.

Expressioni

Gene expression databases

BgeeiENSRNOG00000019368.

Interactioni

Subunit structurei

Heterotrimer containing an alpha/SCNN1A, a beta/SCNN1B and a gamma/SCNN1G subunit. An additional delta/SCNN1D subunit exists only in some organisms and can replace the alpha/SCNN1A subunit to form an alternative channel with specific properties (By similarity). Interacts with NEDD4 (via WW domains) (PubMed:11323714). Interacts with NEDD4L (via WW domains) (PubMed:14556380). Interacts with WWP1 (via WW domains) (By similarity). Interacts with WWP2 (via WW domains) (By similarity). Interacts with the full length immature form of PCSK9 (pro-PCSK9) (By similarity).By similarity2 Publications

GO - Molecular functioni

  • actin binding Source: RGD
  • WW domain binding Source: RGD

Protein-protein interaction databases

BioGridi247193. 2 interactors.
DIPiDIP-61308N.
IntActiP37089. 2 interactors.
STRINGi10116.ENSRNOP00000061813.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4294. Eukaryota.
ENOG410ZNFK. LUCA.
HOVERGENiHBG058435.
InParanoidiP37089.
KOiK04824.
OMAiIFYPKPK.
PhylomeDBiP37089.

Family and domain databases

InterProiIPR004724. ENaC.
IPR001873. Na+channel_ASC.
IPR020903. Na+channel_ASC_CS.
[Graphical view]
PANTHERiPTHR11690. PTHR11690. 2 hits.
PfamiPF00858. ASC. 1 hit.
[Graphical view]
PRINTSiPR01078. AMINACHANNEL.
TIGRFAMsiTIGR00859. ENaC. 1 hit.
PROSITEiPS01206. ASC. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P37089-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLDHTRAPEL NIDLDLHASN SPKGSMKGNQ FKEQDPCPPQ PMQGLGKGDK
60 70 80 90 100
REEQGLGPEP SAPRQPTEEE EALIEFHRSY RELFQFFCNN TTIHGAIRLV
110 120 130 140 150
CSKHNRMKTA FWAVLWLCTF GMMYWQFALL FEEYLSYPVS LNINLNSDKL
160 170 180 190 200
VFPAVTVCTL NPYRYTEIKE ELEELDRITE QTLFDLYKYN SSYTRQAGAR
210 220 230 240 250
RRSSRDLLGA FPHPLQRLRT PPPPYSGRTA RSGSSSVRDN NPQVDRKDWK
260 270 280 290 300
IGFQLCNQNK SDCFYQTYSS GVDAVREWYR FHYINILSRL SDTSPALEEE
310 320 330 340 350
ALGNFIFTCR FNQAPCNQAN YSKFHHPMYG NCYTFNDKNN SNLWMSSMPG
360 370 380 390 400
VNNGLSLTLR TEQNDFIPLL STVTGARVMV HGQDEPAFMD DGGFNLRPGV
410 420 430 440 450
ETSISMRKEA LDSLGGNYGD CTENGSDVPV KNLYPSKYTQ QVCIHSCFQE
460 470 480 490 500
NMIKKCGCAY IFYPKPKGVE FCDYRKQSSW GYCYYKLQGA FSLDSLGCFS
510 520 530 540 550
KCRKPCSVIN YKLSAGYSRW PSVKSQDWIF EMLSLQNNYT INNKRNGVAK
560 570 580 590 600
LNIFFKELNY KTNSESPSVT MVSLLSNLGS QWSLWFGSSV LSVVEMAELI
610 620 630 640 650
FDLLVITLLM LLRRFRSRYW SPGRGARGAR EVASTPASSF PSRFCPHPTS
660 670 680 690
PPPSLPQQGM TPPLALTAPP PAYATLGPSA PPLDSAAPDC SACALAAL
Length:698
Mass (Da):78,888
Last modified:December 1, 2000 - v2
Checksum:iB0CF7C15C3CE9763
GO

Sequence cautioni

The sequence CAA49916 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti598 – 599EL → DV in CAA49905 (PubMed:8381523).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X70521 mRNA. Translation: CAA49916.1. Different initiation.
X70497 mRNA. Translation: CAA49905.1.
U54699 mRNA. Translation: AAB61156.1.
U54700 mRNA. Translation: AAB61157.1.
AF081783 Genomic DNA. Translation: AAD16017.1.
AF082073 mRNA. Translation: AAD16026.1.
PIRiS29499.
RefSeqiNP_113736.1. NM_031548.2.
UniGeneiRn.9808.

Genome annotation databases

GeneIDi25122.
KEGGirno:25122.
UCSCiRGD:3639. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X70521 mRNA. Translation: CAA49916.1. Different initiation.
X70497 mRNA. Translation: CAA49905.1.
U54699 mRNA. Translation: AAB61156.1.
U54700 mRNA. Translation: AAB61157.1.
AF081783 Genomic DNA. Translation: AAD16017.1.
AF082073 mRNA. Translation: AAD16026.1.
PIRiS29499.
RefSeqiNP_113736.1. NM_031548.2.
UniGeneiRn.9808.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247193. 2 interactors.
DIPiDIP-61308N.
IntActiP37089. 2 interactors.
STRINGi10116.ENSRNOP00000061813.

PTM databases

iPTMnetiP37089.
PhosphoSitePlusiP37089.

Proteomic databases

PaxDbiP37089.
PRIDEiP37089.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25122.
KEGGirno:25122.
UCSCiRGD:3639. rat.

Organism-specific databases

CTDi6337.
RGDi3639. Scnn1a.

Phylogenomic databases

eggNOGiKOG4294. Eukaryota.
ENOG410ZNFK. LUCA.
HOVERGENiHBG058435.
InParanoidiP37089.
KOiK04824.
OMAiIFYPKPK.
PhylomeDBiP37089.

Miscellaneous databases

PROiP37089.

Gene expression databases

BgeeiENSRNOG00000019368.

Family and domain databases

InterProiIPR004724. ENaC.
IPR001873. Na+channel_ASC.
IPR020903. Na+channel_ASC_CS.
[Graphical view]
PANTHERiPTHR11690. PTHR11690. 2 hits.
PfamiPF00858. ASC. 1 hit.
[Graphical view]
PRINTSiPR01078. AMINACHANNEL.
TIGRFAMsiTIGR00859. ENaC. 1 hit.
PROSITEiPS01206. ASC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSCNNA_RAT
AccessioniPrimary (citable) accession number: P37089
Secondary accession number(s): Q64593, Q9QUI4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: December 1, 2000
Last modified: November 2, 2016
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.