SCNN1A

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. 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.2 Publications

Enzyme regulationⁱ

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

GO - Molecular functionⁱ

ligand-gated sodium channel activity Source: InterPro
WW domain binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 10642508

Complete GO annotation...

GO - Biological processⁱ

ion transmembrane transport Source: Reactome
multicellular organismal water homeostasis
Source: UniProtKB
Inferred from direct assayⁱ
- 24124190
response to stimulus Source: UniProtKB-KW
sensory perception of taste Source: UniProtKB-KW
sodium ion homeostasis
Source: UniProtKB
Inferred from direct assayⁱ
- 24124190
sodium ion transmembrane transport
Source: UniProtKB
Inferred from direct assayⁱ
- 24124190

Complete GO annotation...

Keywordsⁱ

Molecular function	Ion channel, Sodium channel
Biological process	Ion transport, Sensory transduction, Sodium transport, Taste, Transport
Ligand	Sodium

Enzyme and pathway databases

Reactomeⁱ	R-HSA-2672351. Stimuli-sensing channels.
SIGNORⁱ	P37088.

Protein family/group databases

TCDBⁱ	1.A.6.1.1. the epithelial na(+) channel (enac) family.

TCDBⁱ

1.A.6.1.1. the epithelial na(+) channel (enac) family.

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 Short name: ENaCA Nonvoltage-gated sodium channel 1 subunit alpha SCNEA
Gene namesⁱ	Name:SCNN1A Synonyms:SCNN1
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 12

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:10599. SCNN1A.

HGNCⁱ

HGNC:10599. SCNN1A.

Subcellular locationⁱ

Note:

In the oviduct and bronchus, located on cilia in multi-ciliated cells. In endometrial non-ciliated epithelial cells, restricted to apical surfaces.2 Publications

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	1 – 85	CytoplasmicBy similarityAdd BLAST	85
Transmembraneⁱ	86 – 106	Helical; Name=1Sequence analysisAdd BLAST	21
Topological domainⁱ	107 – 562	ExtracellularBy similarityAdd BLAST	456
Transmembraneⁱ	563 – 583	Helical; Name=2Sequence analysisAdd BLAST	21
Topological domainⁱ	584 – 669	CytoplasmicBy similarityAdd BLAST	86

GO - Cellular componentⁱ

apical plasma membrane
Source: UniProtKB
Inferred from direct assayⁱ
- 22207244
ciliary membrane
Source: UniProtKB
Inferred from direct assayⁱ
- 22207244
extracellular exosome
Source: UniProtKB
Inferred from direct assayⁱ
- 15326289
integral component of plasma membrane
Source: UniProtKB
Inferred from direct assayⁱ
- 24124190
motile cilium
Source: UniProtKB
Inferred from direct assayⁱ
- 22207244
plasma membrane Source: Reactome
sodium channel complex
Source: UniProtKB
Inferred from direct assayⁱ
- 24124190

Complete GO annotation...

Keywords - Cellular componentⁱ

Cell membrane, Cell projection, Membrane

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Pseudohypoaldosteronism 1, autosomal recessive (PHA1B)3 Publications

The disease is caused by mutations affecting the gene represented in this entry. The degree of channel function impairment differentially affects the renin-aldosterone system and urinary Na/K ratios, resulting in distinct genotype-phenotype relationships in PHA1 patients. Loss-of-function mutations are associated with a severe clinical course and age-dependent hyperactivation of the renin-aldosterone system. This feature is not observed in patients with missense mutations that reduce but do not eliminate channel function. Markedly reduced channel activity results in impaired linear growth and delayed puberty (PubMed:18634878).1 Publication

Disease descriptionA rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1B is a severe form involving multiple organ systems, and characterized by an often fulminant presentation in the neonatal period with dehydration, hyponatremia, hyperkalemia, metabolic acidosis, failure to thrive and weight loss.

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_026518	327	G → C in PHA1B; results in a significant reduction of channel function as compared to wild-type; significantly lowers both Li+ and Na+ ion currents. 2 Publications		1
Natural variantⁱVAR_015834	562	S → L in PHA1B. 1 PublicationCorresponds to variant dbSNP:rs137852635Ensembl.		1

Bronchiectasis with or without elevated sweat chloride 2 (BESC2)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA debilitating respiratory disease characterized by chronic, abnormal dilatation of the bronchi and other cystic fibrosis-like symptoms in the absence of known causes of bronchiectasis (cystic fibrosis, autoimmune diseases, ciliary dyskinesia, common variable immunodeficiency, foreign body obstruction). Clinical features include sub-normal lung function, sinopulmonary infections, chronic productive cough, excessive sputum production, and elevated sweat chloride in some cases.

Keywords - Diseaseⁱ

Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	6337.
MalaCards human disease database More...MalaCardsⁱ	SCNN1A.
MIMⁱ	264350. phenotype. 613021. phenotype.
Open Targets More...OpenTargetsⁱ	ENSG00000111319.
Orphanetⁱ	171876. Generalized pseudohypoaldosteronism type 1. 60033. Idiopathic bronchiectasis.
PharmGKBⁱ	PA305.

Chemistry databases

ChEMBLⁱ	CHEMBL1791.
Drug and drug target database More...DrugBankⁱ	DB00594. Amiloride. DB00384. Triamterene.
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	738.

Polymorphism and mutation databases

BioMutaⁱ	SCNN1A.
DMDMⁱ	585966.

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000181261	1 – 669	Amiloride-sensitive sodium channel subunit alphaAdd BLAST		669

Post-translational modificationⁱ

Ubiquitinated; this targets individual subunits for endocytosis and proteasome-mediated degradation.By similarity

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.1 Publication

N-glycosylated.By similarity

Keywords - PTMⁱ

Glycoprotein, Ubl conjugation

Proteomic databases

EPDⁱ	P37088.
PaxDbⁱ	P37088.
PeptideAtlas More...PeptideAtlasⁱ	P37088.
PRIDEⁱ	P37088.

PTM databases

iPTMnetⁱ	P37088.
PhosphoSitePlusⁱ	P37088.

Expressionⁱ

Tissue specificityⁱ

Expressed in the female reproductive tract, from the fimbrial end of the fallopian tube to the endometrium (at protein level). Expressed in kidney (at protein level). In the respiratory tract, expressed in the bronchial epithelium (at protein level). Highly expressed in lung. Detected at intermediate levels in pancreas and liver, and at low levels in heart and placenta. Isoform 1 and isoform 2 predominate in all tissues. Expression of isoform 3, isoform 4 and isoform 5 is very low or not detectable, except in lung and heart.2 Publications

Inductionⁱ

By aldosterone.1 Publication

Gene expression databases

Bgeeⁱ	ENSG00000111319.
CleanExⁱ	HS_SCNN1A.
ExpressionAtlasⁱ	P37088. baseline and differential.
Genevisibleⁱ	P37088. HS.

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA012743.

HPAⁱ

HPA012743.

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:11244092, PubMed:11696533, PubMed:12167593, PubMed:23665454). Interacts with NEDD4L (via WW domains) (PubMed:11244092, PubMed:11696533). Interacts with WWP1 (via WW domains) (PubMed:9169421). Interacts with WWP2 (via WW domains) (PubMed:12167593, PubMed:9169421). Interacts with the full length immature form of PCSK9 (pro-PCSK9) (PubMed:22493497).By similarity6 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
SCNN1G	P51170	3	EBI-7845444,EBI-2547354

With

Entry

#Exp.

IntAct

Notes

SCNN1G

P51170

3

EBI-7845444,EBI-2547354

GO - Molecular functionⁱ

WW domain binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 10642508

Complete GO annotation...

Protein-protein interaction databases

BioGridⁱ	112241. 23 interactors.
IntActⁱ	P37088. 3 interactors.
Molecular INTeraction database More...MINTⁱ	MINT-198663.
STRINGⁱ	9606.ENSP00000353292.

Chemistry databases

BindingDBⁱ

P37088.

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Show more details

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Helixⁱ	644 – 647	Combined sources		4

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2M3O	NMR	-	P	638-648	[»]
ProteinModelPortalⁱ	P37088.
SMRⁱ	P37088.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Sequence similaritiesⁱ

Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1A subfamily. [View classification]Curated

Keywords - Domainⁱ

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG4294. Eukaryota. ENOG410ZNFK. LUCA.
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000119120.
HOGENOMⁱ	HOG000236286.
HOVERGENⁱ	HBG058435.
InParanoidⁱ	P37088.
KEGG Orthology (KO) More...KOⁱ	K04824.
OMAⁱ	VEYCDYR.
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0KW6.
PhylomeDBⁱ	P37088.
TreeFamⁱ	TF330663.

Family and domain databases

InterProⁱ	View protein in InterPro IPR001873. ENaC. IPR004724. ENaC_chordates. IPR020903. ENaC_CS.
PANTHERⁱ	PTHR11690. PTHR11690. 1 hit.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00858. ASC. 1 hit.
PRINTSⁱ	PR01078. AMINACHANNEL.
TIGRFAMsⁱ	TIGR00859. ENaC. 1 hit.
PROSITEⁱ	View protein in PROSITE PS01206. ASC. 1 hit.

Sequences (6)ⁱ

Sequence statusⁱ: Complete.

This entry describes 6 isoformsⁱ produced by alternative splicing. Align Add to basket Added to basket

Isoform 1 (identifier: P37088-1) [UniParc]FASTA Add to basket

Also known as: Alpha ENAC1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEGNKLEEQD SSPPQSTPGL MKGNKREEQG LGPEPAAPQQ PTAEEEALIE 
        60         70         80         90        100
FHRSYRELFE FFCNNTTIHG AIRLVCSQHN RMKTAFWAVL WLCTFGMMYW 
       110        120        130        140        150
QFGLLFGEYF SYPVSLNINL NSDKLVFPAV TICTLNPYRY PEIKEELEEL 
       160        170        180        190        200
DRITEQTLFD LYKYSSFTTL VAGSRSRRDL RGTLPHPLQR LRVPPPPHGA 
       210        220        230        240        250
RRARSVASSL RDNNPQVDWK DWKIGFQLCN QNKSDCFYQT YSSGVDAVRE 
       260        270        280        290        300
WYRFHYINIL SRLPETLPSL EEDTLGNFIF ACRFNQVSCN QANYSHFHHP 
       310        320        330        340        350
MYGNCYTFND KNNSNLWMSS MPGINNGLSL MLRAEQNDFI PLLSTVTGAR 
       360        370        380        390        400
VMVHGQDEPA FMDDGGFNLR PGVETSISMR KETLDRLGGD YGDCTKNGSD 
       410        420        430        440        450
VPVENLYPSK YTQQVCIHSC FQESMIKECG CAYIFYPRPQ NVEYCDYRKH 
       460        470        480        490        500
SSWGYCYYKL QVDFSSDHLG CFTKCRKPCS VTSYQLSAGY SRWPSVTSQE 
       510        520        530        540        550
WVFQMLSRQN NYTVNNKRNG VAKVNIFFKE LNYKTNSESP SVTMVTLLSN 
       560        570        580        590        600
LGSQWSLWFG SSVLSVVEMA ELVFDLLVIM FLMLLRRFRS RYWSPGRGGR 
       610        620        630        640        650
GAQEVASTLA SSPPSHFCPH PMSLSLSQPG PAPSPALTAP PPAYATLGPR 
       660 
PSPGGSAGAS SSTCPLGGP

Length:669

Mass (Da):75,704

Last modified:October 1, 1994 - v1

Checksum:ⁱ2CCF342E7DF32E72

GO

Isoform 2 (identifier: P37088-2) [UniParc]FASTA Add to basket

Also known as: Alpha ENAC2

The sequence of this isoform differs from the canonical sequence as follows:
1-1: M → MGMARGSLTRVPGVMGEGTQGPELSLDPDPCSPQSTPGLMKGNKLEEQDPRPLQPIPGLM

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        10         20         30         40         50
MGMARGSLTR VPGVMGEGTQ GPELSLDPDP CSPQSTPGLM KGNKLEEQDP 
        60         70         80         90        100
RPLQPIPGLM EGNKLEEQDS SPPQSTPGLM KGNKREEQGL GPEPAAPQQP 
       110        120        130        140        150
TAEEEALIEF HRSYRELFEF FCNNTTIHGA IRLVCSQHNR MKTAFWAVLW 
       160        170        180        190        200
LCTFGMMYWQ FGLLFGEYFS YPVSLNINLN SDKLVFPAVT ICTLNPYRYP 
       210        220        230        240        250
EIKEELEELD RITEQTLFDL YKYSSFTTLV AGSRSRRDLR GTLPHPLQRL 
       260        270        280        290        300
RVPPPPHGAR RARSVASSLR DNNPQVDWKD WKIGFQLCNQ NKSDCFYQTY 
       310        320        330        340        350
SSGVDAVREW YRFHYINILS RLPETLPSLE EDTLGNFIFA CRFNQVSCNQ 
       360        370        380        390        400
ANYSHFHHPM YGNCYTFNDK NNSNLWMSSM PGINNGLSLM LRAEQNDFIP 
       410        420        430        440        450
LLSTVTGARV MVHGQDEPAF MDDGGFNLRP GVETSISMRK ETLDRLGGDY 
       460        470        480        490        500
GDCTKNGSDV PVENLYPSKY TQQVCIHSCF QESMIKECGC AYIFYPRPQN 
       510        520        530        540        550
VEYCDYRKHS SWGYCYYKLQ VDFSSDHLGC FTKCRKPCSV TSYQLSAGYS 
       560        570        580        590        600
RWPSVTSQEW VFQMLSRQNN YTVNNKRNGV AKVNIFFKEL NYKTNSESPS 
       610        620        630        640        650
VTMVTLLSNL GSQWSLWFGS SVLSVVEMAE LVFDLLVIMF LMLLRRFRSR 
       660        670        680        690        700
YWSPGRGGRG AQEVASTLAS SPPSHFCPHP MSLSLSQPGP APSPALTAPP 
       710        720 
PAYATLGPRP SPGGSAGASS STCPLGGP

Show »

Length:728

Mass (Da):81,856

Checksum:ⁱ206613374DFB1800

GO

Isoform 3 (identifier: P37088-3) [UniParc]FASTA Add to basket

Also known as: Alpha ENACx

The sequence of this isoform differs from the canonical sequence as follows:
229-245: CNQNKSDCFYQTYSSGV → ELLSLPPPDVWKLLYFG
246-669: Missing.

« Hide

        10         20         30         40         50
MEGNKLEEQD SSPPQSTPGL MKGNKREEQG LGPEPAAPQQ PTAEEEALIE 
        60         70         80         90        100
FHRSYRELFE FFCNNTTIHG AIRLVCSQHN RMKTAFWAVL WLCTFGMMYW 
       110        120        130        140        150
QFGLLFGEYF SYPVSLNINL NSDKLVFPAV TICTLNPYRY PEIKEELEEL 
       160        170        180        190        200
DRITEQTLFD LYKYSSFTTL VAGSRSRRDL RGTLPHPLQR LRVPPPPHGA 
       210        220        230        240 
RRARSVASSL RDNNPQVDWK DWKIGFQLEL LSLPPPDVWK LLYFG

Note: Does not give rise to amiloride-sensitive ion current. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Show »

Length:245

Mass (Da):28,328

Checksum:ⁱFFDC0622FFA37329

GO

Isoform 4 (identifier: P37088-4) [UniParc]FASTA Add to basket

Also known as: Alpha ENAC-19

The sequence of this isoform differs from the canonical sequence as follows:
327-345: Missing.

« Hide

        10         20         30         40         50
MEGNKLEEQD SSPPQSTPGL MKGNKREEQG LGPEPAAPQQ PTAEEEALIE 
        60         70         80         90        100
FHRSYRELFE FFCNNTTIHG AIRLVCSQHN RMKTAFWAVL WLCTFGMMYW 
       110        120        130        140        150
QFGLLFGEYF SYPVSLNINL NSDKLVFPAV TICTLNPYRY PEIKEELEEL 
       160        170        180        190        200
DRITEQTLFD LYKYSSFTTL VAGSRSRRDL RGTLPHPLQR LRVPPPPHGA 
       210        220        230        240        250
RRARSVASSL RDNNPQVDWK DWKIGFQLCN QNKSDCFYQT YSSGVDAVRE 
       260        270        280        290        300
WYRFHYINIL SRLPETLPSL EEDTLGNFIF ACRFNQVSCN QANYSHFHHP 
       310        320        330        340        350
MYGNCYTFND KNNSNLWMSS MPGINNVTGA RVMVHGQDEP AFMDDGGFNL 
       360        370        380        390        400
RPGVETSISM RKETLDRLGG DYGDCTKNGS DVPVENLYPS KYTQQVCIHS 
       410        420        430        440        450
CFQESMIKEC GCAYIFYPRP QNVEYCDYRK HSSWGYCYYK LQVDFSSDHL 
       460        470        480        490        500
GCFTKCRKPC SVTSYQLSAG YSRWPSVTSQ EWVFQMLSRQ NNYTVNNKRN 
       510        520        530        540        550
GVAKVNIFFK ELNYKTNSES PSVTMVTLLS NLGSQWSLWF GSSVLSVVEM 
       560        570        580        590        600
AELVFDLLVI MFLMLLRRFR SRYWSPGRGG RGAQEVASTL ASSPPSHFCP 
       610        620        630        640        650
HPMSLSLSQP GPAPSPALTA PPPAYATLGP RPSPGGSAGA SSSTCPLGGP

Note: Amiloride-sensitive ion current is nearly abolished.

Show »

Length:650

Mass (Da):73,603

Checksum:ⁱ5866D42CCAF6F8B4

GO

Isoform 5 (identifier: P37088-5) [UniParc]FASTA Add to basket

Also known as: Alpha ENAC+22

The sequence of this isoform differs from the canonical sequence as follows:
454-454: G → GQVRSLTPVIPALWEAEAGGSRG

« Hide

        10         20         30         40         50
MEGNKLEEQD SSPPQSTPGL MKGNKREEQG LGPEPAAPQQ PTAEEEALIE 
        60         70         80         90        100
FHRSYRELFE FFCNNTTIHG AIRLVCSQHN RMKTAFWAVL WLCTFGMMYW 
       110        120        130        140        150
QFGLLFGEYF SYPVSLNINL NSDKLVFPAV TICTLNPYRY PEIKEELEEL 
       160        170        180        190        200
DRITEQTLFD LYKYSSFTTL VAGSRSRRDL RGTLPHPLQR LRVPPPPHGA 
       210        220        230        240        250
RRARSVASSL RDNNPQVDWK DWKIGFQLCN QNKSDCFYQT YSSGVDAVRE 
       260        270        280        290        300
WYRFHYINIL SRLPETLPSL EEDTLGNFIF ACRFNQVSCN QANYSHFHHP 
       310        320        330        340        350
MYGNCYTFND KNNSNLWMSS MPGINNGLSL MLRAEQNDFI PLLSTVTGAR 
       360        370        380        390        400
VMVHGQDEPA FMDDGGFNLR PGVETSISMR KETLDRLGGD YGDCTKNGSD 
       410        420        430        440        450
VPVENLYPSK YTQQVCIHSC FQESMIKECG CAYIFYPRPQ NVEYCDYRKH 
       460        470        480        490        500
SSWGQVRSLT PVIPALWEAE AGGSRGYCYY KLQVDFSSDH LGCFTKCRKP 
       510        520        530        540        550
CSVTSYQLSA GYSRWPSVTS QEWVFQMLSR QNNYTVNNKR NGVAKVNIFF 
       560        570        580        590        600
KELNYKTNSE SPSVTMVTLL SNLGSQWSLW FGSSVLSVVE MAELVFDLLV 
       610        620        630        640        650
IMFLMLLRRF RSRYWSPGRG GRGAQEVAST LASSPPSHFC PHPMSLSLSQ 
       660        670        680        690 
PGPAPSPALT APPPAYATLG PRPSPGGSAG ASSSTCPLGG P

Note: Does not give rise to amiloride-sensitive ion current.

Show »

Length:691

Mass (Da):77,980

Checksum:ⁱ07B981FBE74AE30B

GO

Isoform 6 (identifier: P37088-6) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
1-1: M → MSSIKGNKLEEQDPRPLQPIPGLM

« Hide

        10         20         30         40         50
MSSIKGNKLE EQDPRPLQPI PGLMEGNKLE EQDSSPPQST PGLMKGNKRE 
        60         70         80         90        100
EQGLGPEPAA PQQPTAEEEA LIEFHRSYRE LFEFFCNNTT IHGAIRLVCS 
       110        120        130        140        150
QHNRMKTAFW AVLWLCTFGM MYWQFGLLFG EYFSYPVSLN INLNSDKLVF 
       160        170        180        190        200
PAVTICTLNP YRYPEIKEEL EELDRITEQT LFDLYKYSSF TTLVAGSRSR 
       210        220        230        240        250
RDLRGTLPHP LQRLRVPPPP HGARRARSVA SSLRDNNPQV DWKDWKIGFQ 
       260        270        280        290        300
LCNQNKSDCF YQTYSSGVDA VREWYRFHYI NILSRLPETL PSLEEDTLGN 
       310        320        330        340        350
FIFACRFNQV SCNQANYSHF HHPMYGNCYT FNDKNNSNLW MSSMPGINNG 
       360        370        380        390        400
LSLMLRAEQN DFIPLLSTVT GARVMVHGQD EPAFMDDGGF NLRPGVETSI 
       410        420        430        440        450
SMRKETLDRL GGDYGDCTKN GSDVPVENLY PSKYTQQVCI HSCFQESMIK 
       460        470        480        490        500
ECGCAYIFYP RPQNVEYCDY RKHSSWGYCY YKLQVDFSSD HLGCFTKCRK 
       510        520        530        540        550
PCSVTSYQLS AGYSRWPSVT SQEWVFQMLS RQNNYTVNNK RNGVAKVNIF 
       560        570        580        590        600
FKELNYKTNS ESPSVTMVTL LSNLGSQWSL WFGSSVLSVV EMAELVFDLL 
       610        620        630        640        650
VIMFLMLLRR FRSRYWSPGR GGRGAQEVAS TLASSPPSHF CPHPMSLSLS 
       660        670        680        690 
QPGPAPSPAL TAPPPAYATL GPRPSPGGSA GASSSTCPLG GP

Note: No experimental confirmation available.

Show »

Length:692

Mass (Da):78,234

Checksum:ⁱ3AD7710E69D1BE54

GO

Sequence cautionⁱ

The sequence AAH06526 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_060793	61	F → L in BESC2; hypoactive mutation resulting in reduction of protein expression and a significant decrease of amiloride-sensitive sodium currents. 1 PublicationCorresponds to variant dbSNP:rs61758859Ensembl.	1
Natural variantⁱVAR_060794	114	V → I in BESC2; hyperactive mutation resulting in a significant increase of amiloride-sensitive sodium currents. 1 PublicationCorresponds to variant dbSNP:rs61759861Ensembl.	1
Natural variantⁱVAR_060795	181	R → W Functional polymorphism; significant increase of amiloride-sensitive sodium currents. 2 PublicationsCorresponds to variant dbSNP:rs55797039Ensembl.	1
Natural variantⁱVAR_026518	327	G → C in PHA1B; results in a significant reduction of channel function as compared to wild-type; significantly lowers both Li+ and Na+ ion currents. 2 Publications	1
Natural variantⁱVAR_060796	334	A → T Functional polymorphism; significant decrease of amiloride-sensitive sodium currents. 2 PublicationsCorresponds to variant dbSNP:rs11542844Ensembl.	1
Natural variantⁱVAR_052035	402	P → H. Corresponds to variant dbSNP:rs13306616Ensembl.	1
Natural variantⁱVAR_015833	493	W → R Functional polymorphism; results in a 4-fold increase of amiloride-sensitive sodium currents; found in BESC2 patients at higher frequency than in controls; associated with an increased risk for ischemic cerebrovascular events. 2 PublicationsCorresponds to variant dbSNP:rs5742912Ensembl.	1
Natural variantⁱVAR_015834	562	S → L in PHA1B. 1 PublicationCorresponds to variant dbSNP:rs137852635Ensembl.	1
Natural variantⁱVAR_060797	573	V → I. Corresponds to variant dbSNP:rs59142484Ensembl.	1
Natural variantⁱVAR_022142	618	C → F1 PublicationCorresponds to variant dbSNP:rs3741913Ensembl.	1
Natural variantⁱVAR_015835	663	T → A7 PublicationsCorresponds to variant dbSNP:rs2228576Ensembl.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_007719	1	M → MGMARGSLTRVPGVMGEGTQ GPELSLDPDPCSPQSTPGLM KGNKLEEQDPRPLQPIPGLM in isoform 2. Curated	1
Alternative sequenceⁱVSP_043667	1	M → MSSIKGNKLEEQDPRPLQPI PGLM in isoform 6. 1 Publication	1
Alternative sequenceⁱVSP_007720	229 – 245	CNQNK…YSSGV → ELLSLPPPDVWKLLYFG in isoform 3. CuratedAdd BLAST	17
Alternative sequenceⁱVSP_007721	246 – 669	Missing in isoform 3. CuratedAdd BLAST	424
Alternative sequenceⁱVSP_007722	327 – 345	Missing in isoform 4. CuratedAdd BLAST	19
Alternative sequenceⁱVSP_007723	454	G → GQVRSLTPVIPALWEAEAGG SRG in isoform 5. Curated	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	X76180 mRNA. Translation: CAA53773.1. L29007 Genomic DNA. Translation: AAA21813.1. Z92978 , Z92979, Z92980, Z92981 Genomic DNA. Translation: CAB07505.1. AF060913 , AF060910, AF060911, AF060912 Genomic DNA. Translation: AAD28355.1. DQ402522 mRNA. Translation: ABD72218.1. AK304379 mRNA. Translation: BAG65217.1. FJ515830 Genomic DNA. Translation: ACS13721.1. AC005840 Genomic DNA. No translation available. AC006057 Genomic DNA. No translation available. CH471116 Genomic DNA. Translation: EAW88804.1. BC006526 mRNA. Translation: AAH06526.2. Different initiation. BC062613 mRNA. Translation: AAH62613.1. U81961 Genomic DNA. Translation: AAC31773.1. U81961 Genomic DNA. Translation: AAC31774.1.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS53738.1. [P37088-2] CCDS53739.1. [P37088-6] CCDS8543.1. [P37088-1]
PIRⁱ	A49585.
NCBI Reference Sequences More...RefSeqⁱ	NP_001029.1. NM_001038.5. [P37088-1] NP_001153047.1. NM_001159575.1. [P37088-6] NP_001153048.1. NM_001159576.1. [P37088-2]
UniGeneⁱ	Hs.591047.

Genome annotation databases

Ensemblⁱ	ENST00000228916; ENSP00000228916; ENSG00000111319. [P37088-1] ENST00000360168; ENSP00000353292; ENSG00000111319. [P37088-2] ENST00000543768; ENSP00000438739; ENSG00000111319. [P37088-6]
GeneIDⁱ	6337.
KEGGⁱ	hsa:6337.
UCSC genome browser More...UCSCⁱ	uc001qnw.3. human. [P37088-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

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.

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	X76180 mRNA. Translation: CAA53773.1. L29007 Genomic DNA. Translation: AAA21813.1. Z92978 , Z92979, Z92980, Z92981 Genomic DNA. Translation: CAB07505.1. AF060913 , AF060910, AF060911, AF060912 Genomic DNA. Translation: AAD28355.1. DQ402522 mRNA. Translation: ABD72218.1. AK304379 mRNA. Translation: BAG65217.1. FJ515830 Genomic DNA. Translation: ACS13721.1. AC005840 Genomic DNA. No translation available. AC006057 Genomic DNA. No translation available. CH471116 Genomic DNA. Translation: EAW88804.1. BC006526 mRNA. Translation: AAH06526.2. Different initiation. BC062613 mRNA. Translation: AAH62613.1. U81961 Genomic DNA. Translation: AAC31773.1. U81961 Genomic DNA. Translation: AAC31774.1.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS53738.1. [P37088-2] CCDS53739.1. [P37088-6] CCDS8543.1. [P37088-1]
PIRⁱ	A49585.
NCBI Reference Sequences More...RefSeqⁱ	NP_001029.1. NM_001038.5. [P37088-1] NP_001153047.1. NM_001159575.1. [P37088-6] NP_001153048.1. NM_001159576.1. [P37088-2]
UniGeneⁱ	Hs.591047.

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2M3O	NMR	-	P	638-648	[»]
ProteinModelPortalⁱ	P37088.
SMRⁱ	P37088.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	112241. 23 interactors.
IntActⁱ	P37088. 3 interactors.
Molecular INTeraction database More...MINTⁱ	MINT-198663.
STRINGⁱ	9606.ENSP00000353292.

Chemistry databases

BindingDBⁱ	P37088.
ChEMBLⁱ	CHEMBL1791.
Drug and drug target database More...DrugBankⁱ	DB00594. Amiloride. DB00384. Triamterene.
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	738.

Protein family/group databases

TCDBⁱ	1.A.6.1.1. the epithelial na(+) channel (enac) family.

TCDBⁱ

1.A.6.1.1. the epithelial na(+) channel (enac) family.

PTM databases

iPTMnetⁱ	P37088.
PhosphoSitePlusⁱ	P37088.

Polymorphism and mutation databases

BioMutaⁱ	SCNN1A.
DMDMⁱ	585966.

Proteomic databases

EPDⁱ	P37088.
PaxDbⁱ	P37088.
PeptideAtlas More...PeptideAtlasⁱ	P37088.
PRIDEⁱ	P37088.

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000228916; ENSP00000228916; ENSG00000111319. [P37088-1] ENST00000360168; ENSP00000353292; ENSG00000111319. [P37088-2] ENST00000543768; ENSP00000438739; ENSG00000111319. [P37088-6]
GeneIDⁱ	6337.
KEGGⁱ	hsa:6337.
UCSC genome browser More...UCSCⁱ	uc001qnw.3. human. [P37088-1]

Organism-specific databases

CTDⁱ	6337.
DisGeNET More...DisGeNETⁱ	6337.
GeneCardsⁱ	SCNN1A.
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:10599. SCNN1A.
Human Protein Atlas More...HPAⁱ	HPA012743.
MalaCards human disease database More...MalaCardsⁱ	SCNN1A.
MIMⁱ	264350. phenotype. 600228. gene. 613021. phenotype.
neXtProtⁱ	NX_P37088.
Open Targets More...OpenTargetsⁱ	ENSG00000111319.
Orphanetⁱ	171876. Generalized pseudohypoaldosteronism type 1. 60033. Idiopathic bronchiectasis.
PharmGKBⁱ	PA305.
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG4294. Eukaryota. ENOG410ZNFK. LUCA.
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00760000119120.
HOGENOMⁱ	HOG000236286.
HOVERGENⁱ	HBG058435.
InParanoidⁱ	P37088.
KEGG Orthology (KO) More...KOⁱ	K04824.
OMAⁱ	VEYCDYR.
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0KW6.
PhylomeDBⁱ	P37088.
TreeFamⁱ	TF330663.

Enzyme and pathway databases

Reactomeⁱ	R-HSA-2672351. Stimuli-sensing channels.
SIGNORⁱ	P37088.

Miscellaneous databases

ChiTaRSⁱ	SCNN1A. human.
GeneWikiⁱ	SCNN1A.
GenomeRNAiⁱ	6337.
Protein Ontology More...PROⁱ	PR:P37088.
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000111319.
CleanExⁱ	HS_SCNN1A.
ExpressionAtlasⁱ	P37088. baseline and differential.
Genevisibleⁱ	P37088. HS.

Family and domain databases

InterProⁱ	View protein in InterPro IPR001873. ENaC. IPR004724. ENaC_chordates. IPR020903. ENaC_CS.
PANTHERⁱ	PTHR11690. PTHR11690. 1 hit.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00858. ASC. 1 hit.
PRINTSⁱ	PR01078. AMINACHANNEL.
TIGRFAMsⁱ	TIGR00859. ENaC. 1 hit.
PROSITEⁱ	View protein in PROSITE PS01206. ASC. 1 hit.
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	SCNNA_HUMAN
Accessionⁱ	P37088Primary (citable) accession number: P37088 Secondary accession number(s): A5X2U9 , B4E2Q5, C5HTZ0, O43271, Q6GSQ6, Q9UM64
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
	Last sequence update:	October 1, 1994
	Last modified:	July 5, 2017
	This is version 182 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
SIMILARITY comments
Index of protein domains and families

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UniProtKB - P37088 (SCNNA_HUMAN)

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Amiloride-sensitive sodium channel subunit alpha

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>This subsection of the ‘Function’ section describes an enzyme regulatory mechanism and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/enzyme_regulation' target='_top'>More...</a></p>Enzyme regulationi

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (6)i

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

Protein family/group databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Documents

Functionⁱ

Enzyme regulationⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequences (6)ⁱ

Sequence cautionⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ