Gen SCNN1G kod kićmenjaka kodira podjedinicu γ epitelnog natrijevog kanala ENaC . ENaC je sastavljen kao heterotrimer od tri homologne podjedinice α, β i γ ili δ, β i γ. Ostale ENAC podjedinice su kodirane pomoću SCNN1A, SCNN1B i SCNN1D.[5]

SCNN1G
Identifikatori
AliasiSCNN1G
Vanjski ID-jeviOMIM: 600761 MGI: 104695 HomoloGene: 20280 GeneCards: SCNN1G
Lokacija gena (čovjek)
Hromosom 16 (čovjek)
Hrom.Hromosom 16 (čovjek)[1]
Hromosom 16 (čovjek)
Genomska lokacija za SCNN1G
Genomska lokacija za SCNN1G
Bend16p12.2Početak23,182,745 bp[1]
Kraj23,216,883 bp[1]
Lokacija gena (miš)
Hromosom 7 (miš)
Hrom.Hromosom 7 (miš)[2]
Hromosom 7 (miš)
Genomska lokacija za SCNN1G
Genomska lokacija za SCNN1G
Bend7 F2|7 65.07 cMPočetak121,333,702 bp[2]
Kraj121,367,698 bp[2]
Ontologija gena
Molekularna funkcija sodium channel activity
ion channel activity
GO:0001948, GO:0016582 vezivanje za proteine
WW domain binding
ligand-gated sodium channel activity
Ćelijska komponenta integral component of membrane
membrana
sodium channel complex
integral component of plasma membrane
apical plasma membrane
Egzosom
external side of plasma membrane
nukleoplazma
ćelijska membrana
Biološki proces izlučivanje
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
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_001039

NM_011326

RefSeq (bjelančevina)

NP_001030

NP_035456

Lokacija (UCSC)Chr 16: 23.18 – 23.22 MbChr 7: 121.33 – 121.37 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

ENaC se eksprimira u epitelnim ćelijama i razlikuje se od naponski ovisnog natrijwvog kanala koji je uključen u stvaranje akcijskih potencijala u neuronima. Skraćenica za gene koji kodiraju za naponski 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 (SCNN1) predstavlja da se radi o kanalima koji nisu naponski.

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

Pošto amilorid snažno inhibira ENaC, on se takođe naziva "natrijevim kanalom osetljivim na amilorid".

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 649 aminokiselina, a molekulska masa 74.270 Da.[5]

1020304050
MAPGEKIKAKIKKNLPVTGPQAPTIKELMRWYCLNTNTHGCRRIVVSRGR
LRRLLWIGFTLTAVALILWQCALLVFSFYTVSVSIKVHFRKLDFPAVTIC
NINPYKYSTVRHLLADLEQETREALKSLYGFPESRKRREAESWNSVSEGK
QPRFSHRIPLLIFDQDEKGKARDFFTGRKRKVGGSIIHKASNVMHIESKQ
VVGFQLCSNDTSDCATYTFSSGINAIQEWYKLHYMNIMAQVPLEKKINMS
YSAEELLVTCFFDGVSCDARNFTLFHHPMHGNCYTFNNRENETILSTSMG
GSEYGLQVILYINEEEYNPFLVSSTGAKVIIHRQDEYPFVEDVGTEIETA
MVTSIGMHLTESFKLSEPYSQCTEDGSDVPIRNIYNAAYSLQICLHSCFQ
TKMVEKCGCAQYSQPLPPAANYCNYQQHPNWMYCYYQLHRAFVQEELGCQ
SVCKEACSFKEWTLTTSLAQWPSVVSEKWLLPVLTWDQGRQVNKKLNKTD
LAKLLIFYKDLNQRSIMESPANSIEMLLSNFGGQLGLWMSCSVVCVIEII
EVFFIDFFSIIARRQWQKAKEWWAWKQAPPCPEAPRSPQGQDNPALDIDD
DLPTFNSALHLPPALGTQVPGTPPPKYNTLRLERAFSNQLTDTQMLDEL

Struktura gena

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Dok se ljudski gen SCNN1A nalazi u hromosomskoj sekvenci 12p,[8] ljudski geni koji kodiraju SCNN1B i SCNN1G nalaze se u jukstopoziciji u kratkom kraku hromosoma 16 (16p12-p13). Strukture ljudskih i pacovskih SCNN1G gena prvi su objavili Thomas et al.[9][10] Kasnije studije Saxena et al. prijavile su kompletnu kodirajuću sekvencu ljudskog SCNN1G gena, utvrđujući da ima 13 egzona. Položaji introna su konzervirani u sva tri ljudska ENaC gena, SCNN1A, SCNN1B i SCNN1G.[11] The positions of the introns are also highly conserved across vertebrates See: Ensembl GeneTree.

 
Egzon-intron struktura primarnog transkripta ljudskog SCNN1B. Broj svakog egzona je označen iznad njega. Iznad transkripta je prikazan redni broj transkripta. Klikom na sliku će čitatelj biti upućen na listu transkripata u bazi podataka Ensembl.

Struktura proteina

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Primarne strukture sve četiri ENaC podjedinice pokazuju snažnu sličnost. Dakle, ova četiri proteina predstavljaju porodicu proteina koji imaju zajedničkog pretka. U globalnom poravnanju (što znači poravnanje sekvenci duž cele njihove dužine, a ne samo djelimičnog segmenta), ljudska γ podjedinica dijeli 34% identiteta sa β podjedinicom i 27 i 23% identiteta sa α i δ podjedinicama.

Sve četiri sekvence ENaC podjedinica imaju dva hidrofobna dijela koja formiraju dva transmembranska segmenta zvana TM1 i TM2.[12]

Klinički značaj

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Od nasljednih poremećaja ovog gene najozbiljniji je Liddleov sindrom. Općenito je uzrokovan mutacijama u PY motivu ili skraćenjem C-terminala, uključujući gubitak PY motiva u β ili γ ENaC podjedinicama.[13][14][15][16][17][18] Iako postoji PY motiv također u α podjedinici, do sada Liddleova bolest nije uočena u vezi s mutacijom u α podjedinici. Liddleov sindrom se nasljeđuje kao autosomno dominantna bolest s fenotipom koji uključuje hipertenziju u ranom nastanku, metaboličku alkalozu i niske razine aktivnosti renina u plazmi i mineralokortikoidnog hormona aldosterona. U nedostatku prepoznatljivog PY motiva, ubikvitin-proteinska ligaza Nedd4-2 ne može se vezati za ENaC podjedinicu i stoga ne može vezati ubikvitin na nju. Posljedično, proteoliza ENaC proteasomom je inhibirana i ENaC se akumulira u membrani što dovodi do pojačane aktivnosti ENaC koja uzrokuje hipertenziju.[19][20][21][22]

Interakcije

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Pokazalo se da SCNN1G u interakciji sa:

Također pogledajte

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Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000166828 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000216 - 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.
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  28. ^ Raikwar NS, Thomas CP (May 2008). "Nedd4-2 isoforms ubiquitinate individual epithelial sodium channel subunits and reduce surface expression and function of the epithelial sodium channel". Am. J. Physiol. Renal Physiol. 294 (5): F1157–65. doi:10.1152/ajprenal.00339.2007. PMC 2424110. PMID 18322022.

Dopunska literatura

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Vanjski linkovi

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