SCNN1A

SCNN1A je ljudaki gen sa hromosoma 12, kiji kodira α podjedinicu epitelnog natrijevog kanala ENaC u kičmenjacima. ENaC je sastavljen kao heterotrimer od tri homologne podjedinice α, β i γ ili δ, β i γ.^[5] Ostale ENAC podjedinice su kodirane pomoću SCNN1B, SCNN1G i SCNN1D.

SCNN1A
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 2M3O
Identifikatori
Aliasi	SCNN1A
Vanjski ID-jevi	OMIM: 600228 MGI: 101782 HomoloGene: 811 GeneCards: SCNN1A
Lokacija gena (čovjek) Hrom. Hromosom 12 (čovjek)[1] Bend 12p13.31 Početak 6,346,843 bp[1] Kraj 6,377,730 bp[1]
Lokacija gena (miš) Hrom. Hromosom 6 (miš)[2] Bend 6 F3|6 59.32 cM Početak 125,297,622 bp[2] Kraj 125,321,906 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • sodium channel activity • GO:0001948, GO:0016582 vezivanje za proteine • ligand-gated sodium channel activity • WW domain binding Ćelijska komponenta • integral component of membrane • projekcija ćelije • membrana • sodium channel complex • integral component of plasma membrane • Treplja • ciliary membrane • Egzosom • ćelijska membrana • apical plasma membrane • citoplazma • sperm principal piece • Akrozom • GO:0016023 citoplazmatska vezikula • motile cilium Biološki proces • sodium ion transmembrane transport • response to stimulus • sodium ion transport • ion transport • sodium ion homeostasis • multicellular organismal water homeostasis • sensory perception of taste • ion transmembrane transport Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	6337	20276
Ensembl	ENSG00000111319	ENSMUSG00000030340
UniProt	P37088	Q61180
RefSeq (mRNK)	NM_001159576 NM_001038 NM_001159575	NM_011324
RefSeq (bjelančevina)	NP_001029 NP_001153047 NP_001153048	NP_035454 NP_001392957 NP_001392960
Lokacija (UCSC)	Chr 12: 6.35 – 6.38 Mb	Chr 6: 125.3 – 125.32 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

ENaC se eksprimira u epitelnim ćelijama^[5] i razlikuje se od naponskog natrijevog kanala koji je uključen u stvaranje akcijskih potencijala u neuronima. Skraćenica za gene koji kodiraju za voltazijski natrijski kanal počinje sa tri slova: SCN. Za razliku od ovih natrijevih kanala, ENaC je konstitutivno aktivan i ne zavisi od napona. Drugo N u skraćenici (SCNN1A) predstavlja da se radi o kanalima koji nisu naponski.

Kod većine kičmenjaka, ioni natrijuma su glavna determinanta osmolarnosti vanćelijake tečnosti.^[6] ENaC omogućava transfer iona natrija preko ćelijske membrane u epitelu u takozvanim "zategnutim epitelima" koji imaju nisku permeabilnost. Protok iona natrija epitel utiče na osmolarnost ekstracelularne tečnosti. Dakle, ENaC igra centralnu ulogu u regulaciji putem homeostaze tjelesnih tekućina i elektrolita i posljedično utiče na krvni pritisak.^[7]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 669 aminokiselina, a molekulska težina 75.704 Da.^[5]

• C: Cistein
• D: Asparaginska kiselina
• E: Glutaminska kiselina
• F: Fenilalanin
• G: Glicin
• H: Histidin
• I: Izoleucin
• K: Lizin
• L: Leucin
• M: Metionin
• N: Asparagin
• P: Prolin
• Q: Glutamin
• R: Arginin
• S: Serin
• T: Treonin
• V: Valin
• W: Triptofan
• Y: Tirozin

10		20		30		40		50
MEGNKLEEQD		SSPPQSTPGL		MKGNKREEQG		LGPEPAAPQQ		PTAEEEALIE
FHRSYRELFE		FFCNNTTIHG		AIRLVCSQHN		RMKTAFWAVL		WLCTFGMMYW
QFGLLFGEYF		SYPVSLNINL		NSDKLVFPAV		TICTLNPYRY		PEIKEELEEL
DRITEQTLFD		LYKYSSFTTL		VAGSRSRRDL		RGTLPHPLQR		LRVPPPPHGA
RRARSVASSL		RDNNPQVDWK		DWKIGFQLCN		QNKSDCFYQT		YSSGVDAVRE
WYRFHYINIL		SRLPETLPSL		EEDTLGNFIF		ACRFNQVSCN		QANYSHFHHP
MYGNCYTFND		KNNSNLWMSS		MPGINNGLSL		MLRAEQNDFI		PLLSTVTGAR
VMVHGQDEPA		FMDDGGFNLR		PGVETSISMR		KETLDRLGGD		YGDCTKNGSD
VPVENLYPSK		YTQQVCIHSC		FQESMIKECG		CAYIFYPRPQ		NVEYCDYRKH
SSWGYCYYKL		QVDFSSDHLG		CFTKCRKPCS		VTSYQLSAGY		SRWPSVTSQE
WVFQMLSRQN		NYTVNNKRNG		VAKVNIFFKE		LNYKTNSESP		SVTMVTLLSN
LGSQWSLWFG		SSVLSVVEMA		ELVFDLLVIM		FLMLLRRFRS		RYWSPGRGGR
GAQEVASTLA		SSPPSHFCPH		PMSLSLSQPG		PAPSPALTAP		PPAYATLGPR
PSPGGSAGAS		SSTCPLGGP

Interakcije

Pokazalo se da SCNN1A interraguje sa:

• NEDD4L,^[8][9]
• NEDD4,^[8][10][11] i
• Ubikvitin C^[12][13]

Također pogledajte

• Epitelni natrijski kanal

Reference

1. GRCh38: Ensembl release 89: ENSG00000111319 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030340 - Ensembl, maj 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Hanukoglu I, Hanukoglu A (april 2016). "Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases". Gene. 579 (2): 95–132. doi:10.1016/j.gene.2015.12.061. PMC 4756657. PMID 26772908.
6. Bourque CW (juli 2008). "Central mechanisms of osmosensation and systemic osmoregulation". Nature Reviews. Neuroscience. 9 (7): 519–31. doi:10.1038/nrn2400. PMID 18509340. S2CID 205504313.
7. Rossier BC, Baker ME, Studer RA (januar 2015). "Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited". Physiological Reviews. 95 (1): 297–340. doi:10.1152/physrev.00011.2014. PMID 25540145.
8. Harvey KF, Dinudom A, Cook DI, Kumar S (mart 2001). "The Nedd4-like protein KIAA0439 is a potential regulator of the epithelial sodium channel". The Journal of Biological Chemistry. 276 (11): 8597–601. doi:10.1074/jbc.C000906200. PMID 11244092.
9. Malbert-Colas L, Nicolas G, Galand C, Lecomte MC, Dhermy D (juli 2003). "Identification of new partners of the epithelial sodium channel alpha subunit". Comptes Rendus Biologies. 326 (7): 615–24. doi:10.1016/s1631-0691(03)00154-9. PMID 14556380.
10. Farr TJ, Coddington-Lawson SJ, Snyder PM, McDonald FJ (februar 2000). "Human Nedd4 interacts with the human epithelial Na+ channel: WW3 but not WW1 binds to Na+-channel subunits". The Biochemical Journal. 345 Pt 3 (3): 503–9. doi:10.1042/0264-6021:3450503. PMC 1220784. PMID 10642508.
11. McDonald FJ, Western AH, McNeil JD, Thomas BC, Olson DR, Snyder PM (septembar 2002). "Ubiquitin-protein ligase WWP2 binds to and downregulates the epithelial Na(+) channel". American Journal of Physiology. Renal Physiology. 283 (3): F431–6. doi:10.1152/ajprenal.00080.2002. PMID 12167593.
12. Boulkroun S, Ruffieux-Daidié D, Vitagliano JJ, Poirot O, Charles RP, Lagnaz D, Firsov D, Kellenberger S, Staub O (oktobar 2008). "Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell surface expression by deubiquitylating and stabilizing sorting nexin 3". American Journal of Physiology. Renal Physiology. 295 (4): F889–900. doi:10.1152/ajprenal.00001.2008. PMID 18632802.
13. Raikwar NS, Thomas CP (maj 2008). "Nedd4-2 isoforms ubiquitinate individual epithelial sodium channel subunits and reduce surface expression and function of the epithelial sodium channel". American Journal of Physiology. Renal Physiology. 294 (5): F1157–65. doi:10.1152/ajprenal.00339.2007. PMC 2424110. PMID 18322022.

Dopunska literatura

• McDonald FJ, Snyder PM, McCray PB, Welsh MJ (juni 1994). "Cloning, expression, and tissue distribution of a human amiloride-sensitive Na+ channel". The American Journal of Physiology. 266 (6 Pt 1): L728–34. doi:10.1152/ajplung.1994.266.6.L728. PMID 8023962.
• Voilley N, Lingueglia E, Champigny G, Mattéi MG, Waldmann R, Lazdunski M, Barbry P (januar 1994). "The lung amiloride-sensitive Na+ channel: biophysical properties, pharmacology, ontogenesis, and molecular cloning". Proceedings of the National Academy of Sciences of the United States of America. 91 (1): 247–51. Bibcode:1994PNAS...91..247V. doi:10.1073/pnas.91.1.247. PMC 42924. PMID 8278374.
• Harvey KF, Dinudom A, Komwatana P, Jolliffe CN, Day ML, Parasivam G, Cook DI, Kumar S (april 1999). "All three WW domains of murine Nedd4 are involved in the regulation of epithelial sodium channels by intracellular Na+". The Journal of Biological Chemistry. 274 (18): 12525–30. doi:10.1074/jbc.274.18.12525. PMID 10212229.
• Arai K, Zachman K, Shibasaki T, Chrousos GP (juli 1999). "Polymorphisms of amiloride-sensitive sodium channel subunits in five sporadic cases of pseudohypoaldosteronism: do they have pathologic potential?". The Journal of Clinical Endocrinology and Metabolism. 84 (7): 2434–7. doi:10.1210/jcem.84.7.5857. PMID 10404817.
• Saxena S, Quick MW, Tousson A, Oh Y, Warnock DG (juli 1999). "Interaction of syntaxins with the amiloride-sensitive epithelial sodium channel". The Journal of Biological Chemistry. 274 (30): 20812–7. doi:10.1074/jbc.274.30.20812. PMID 10409621.
• Schaedel C, Marthinsen L, Kristoffersson AC, Kornfält R, Nilsson KO, Orlenius B, Holmberg L (decembar 1999). "Lung symptoms in pseudohypoaldosteronism type 1 are associated with deficiency of the alpha-subunit of the epithelial sodium channel". The Journal of Pediatrics. 135 (6): 739–45. doi:10.1016/S0022-3476(99)70094-6. PMID 10586178.
• Snyder PM, Olson DR, McDonald FJ, Bucher DB (juli 2001). "Multiple WW domains, but not the C2 domain, are required for inhibition of the epithelial Na+ channel by human Nedd4". The Journal of Biological Chemistry. 276 (30): 28321–6. doi:10.1074/jbc.M011487200. PMID 11359767.

Vanjski linkovi

• SCNN1A protein, human na US National Library of Medicine Medical Subject Headings (MeSH)