LRRC8D

LRRC8D
Identifikatori
Aliasi	LRRC8D
Vanjski ID-jevi	OMIM: 612890 MGI: 1922368 HomoloGene: 10004 GeneCards: LRRC8D
Lokacija gena (čovjek) Hrom. Hromosom 1 (čovjek)[1] Bend 1p22.2 Početak 89,821,014 bp[1] Kraj 89,936,611 bp[1]
Lokacija gena (miš) Hrom. Hromosom 5 (miš)[2] Bend 5|5 E5 Početak 105,847,835 bp[2] Kraj 105,980,302 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • GO:0001948, GO:0016582 vezivanje za proteine • volume-sensitive anion channel activity Ćelijska komponenta • citoplazma • integral component of membrane • integral component of plasma membrane • endoplasmic reticulum membrane • membrana • Endoplazmatski retikulum • Ionski kanal • ćelijska membrana Biološki proces • anion transmembrane transport • ion transport • regulation of anion transport • GO:0072468 Transdukcija signala • transmembrane transport • GO:0015915 transport • cell volume homeostasis • inorganic anion transport • taurine transport • aspartate transmembrane transport • cellular response to osmotic stress Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	55144	231549
Ensembl	ENSG00000171492	ENSMUSG00000046079
UniProt	Q7L1W4	Q8BGR2
RefSeq (mRNK)	NM_001134479 NM_018103	NM_001122768 NM_178701
RefSeq (bjelančevina)	NP_001127951 NP_060573	NP_001116240 NP_848816
Lokacija (UCSC)	Chr 1: 89.82 – 89.94 Mb	Chr 5: 105.85 – 105.98 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Leucinom-bogati protein sa ponavljanjima proteina 8D jest protein koji je kod ljudi kodiran genom LRRC8D sa hromosoma 1.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 858 aminokiselina, a molekulska težina 98.201 Da.^[6]

• 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
MFTLAEVASL		NDIQPTYRIL		KPWWDVFMDY		LAVVMLMVAI		FAGTMQLTKD
QVVCLPVLPS		PVNSKAHTPP		GNAEVTTNIP		KMEAATNQDQ		DGRTTNDISF
GTSAVTPDIP		LRATYPRTDF		ALPNQEAKKE		KKDPTGRKTN		LDFQQYVFIN
QMCYHLALPW		YSKYFPYLAL		IHTIILMVSS		NFWFKYPKTC		SKVEHFVSIL
GKCFESPWTT		KALSETACED		SEENKQRITG		AQTLPKHVST		SSDEGSPSAS
TPMINKTGFK		FSAEKPVIEV		PSMTILDKKD		GEQAKALFEK		VRKFRAHVED
SDLIYKLYVV		QTVIKTAKFI		FILCYTANFV		NAISFEHVCK		PKVEHLIGYE
VFECTHNMAY		MLKKLLISYI		SIICVYGFIC		LYTLFWLFRI		PLKEYSFEKV
REESSFSDIP		DVKNDFAFLL		HMVDQYDQLY		SKRFGVFLSE		VSENKLREIS
LNHEWTFEKL		RQHISRNAQD		KQELHLFMLS		GVPDAVFDLT		DLDVLKLELI
PEAKIPAKIS		QMTNLQELHL		CHCPAKVEQT		AFSFLRDHLR		CLHVKFTDVA
EIPAWVYLLK		NLRELYLIGN		LNSENNKMIG		LESLRELRHL		KILHVKSNLT
KVPSNITDVA		PHLTKLVIHN		DGTKLLVLNS		LKKMMNVAEL		ELQNCELERI
PHAIFSLSNL		QELDLKSNNI		RTIEEIISFQ		HLKRLTCLKL		WHNKIVTIPP
SITHVKNLES		LYFSNNKLES		LPVAVFSLQK		LRCLDVSYNN		ISMIPIEIGL
LQNLQHLHIT		GNKVDILPKQ		LFKCIKLRTL		NLGQNCITSL		PEKVGQLSQL
TQLELKGNCL		DRLPAQLGQC		RMLKKSGLVV		EDHLFDTLPL		EVKEALNQDI
NIPFANGI

Funkcija

Istraživanja su otkrila da je ovaj protein, zajedno sa ostalim LRRC8 proteinima LRRC8A, LRRC8B, LRRC8C i LRRC8E, podjedinica heteromernog proteina zapreminski reguliranog anionskog kanala.^[7] Ti kanali (VRAC) ključni su za regulaciju veličine ćelije transportom hloridnih iona i raznih organskih osmolita, poput taurina ili glutamata, kroz plazmamembranu,^[8] i to nije jedina funkcija na koju su ovi ionski kanali povezani.

Dok je LRRC8D jedan od mnogih proteina koji mogu biti dio VRAC-a, on je zapravo jedna od najvažnijih podjedinica za sposobnost kanala da funkcionira; drugi važan protein je LRRC8A.^[9][10] Međutim, iako se zna da je neophodan za specifičnu VRAC funkciju, druge studije su otkrile da to nije dovoljno za cijeli raspon uobičajenih aktivnosti VRAC-a.^[11] Tu dolaze drugi proteini LRRC8, jer različit sastav ovih podjedinica utiče na opseg specifičnosti za VRAC-eve.^[12][13]

Pored svoje uloge u VRAC, porodica proteina LRRC8 je takođe povezana sa agamaglobulinemijom-5.^[14]

Reference

1. GRCh38: Ensembl release 89: ENSG00000171492 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000046079 - 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. "Entrez Gene: LRRC8A leucine rich repeat containing 8 family, member A".
6. "UniProt, Q7L1W4" (jezik: eng.). Pristupljeno 30. 11. 2021.
7. Voss FK, Ullrich F, Münch J, Lazarow K, Lutter D, Mah N, Andrade-Navarro MA, von Kries JP, Stauber T, Jentsch TJ (maj 2014). "Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC" (PDF). Science. 344 (6184): 634–8. Bibcode:2014Sci...344..634V. doi:10.1126/science.1252826. PMID 24790029. S2CID 24709412.
8. Jentsch TJ (maj 2016). "VRACs and other ion channels and transporters in the regulation of cell volume and beyond". Nature Reviews Molecular Cell Biology. 17 (5): 293–307. doi:10.1038/nrm.2016.29. PMID 27033257. S2CID 40565653.
9. Hyzinski-García MC, Rudkouskaya A, Mongin AA (novembar 2014). "LRRC8A protein is indispensable for swelling-activated and ATP-induced release of excitatory amino acids in rat astrocytes". The Journal of Physiology. 592 (22): 4855–62. doi:10.1113/jphysiol.2014.278887. PMC 4259531. PMID 25172945.
10. Yamada T, Wondergem R, Morrison R, Yin VP, Strange K (oktobar 2016). "Leucine-rich repeat containing protein LRRC8A is essential for swelling-activated Cl- currents and embryonic development in zebrafish". Physiological Reports. 4 (19): e12940. doi:10.14814/phy2.12940. PMC 5064130. PMID 27688432.
11. Okada T, Islam MR, Tsiferova NA, Okada Y, Sabirov RZ (mart 2017). "Specific and essential but not sufficient roles of LRRC8A in the activity of volume-sensitive outwardly rectifying anion channel (VSOR)". Channels. 11 (2): 109–120. doi:10.1080/19336950.2016.1247133. PMC 5398601. PMID 27764579.
12. Lutter D, Ullrich F, Lueck JC, Kempa S, Jentsch TJ (mart 2017). "Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels". Journal of Cell Science. 130 (6): 1122–1133. doi:10.1242/jcs.196253. PMID 28193731.
13. Planells-Cases R, Lutter D, Guyader C, Gerhards NM, Ullrich F, Elger DA, Kucukosmanoglu A, Xu G, Voss FK, Reincke SM, Stauber T, Blomen VA, Vis DJ, Wessels LF, Brummelkamp TR, Borst P, Rottenberg S, Jentsch TJ (decembar 2015). "Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs". The EMBO Journal. 34 (24): 2993–3008. doi:10.15252/embj.201592409. PMC 4687416. PMID 26530471.
14. Sawada A, Takihara Y, Kim JY, Matsuda-Hashii Y, Tokimasa S, Fujisaki H, Kubota K, Endo H, Onodera T, Ohta H, Ozono K, Hara J (decembar 2003). "A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans". The Journal of Clinical Investigation. 112 (11): 1707–13. doi:10.1172/JCI18937. PMC 281644. PMID 14660746.

Dopunska literatura

• Eggermont J, Trouet D, Carton I, Nilius B (2001). "Cellular function and control of volume-regulated anion channels". Cell Biochemistry and Biophysics. 35 (3): 263–74. doi:10.1385/CBB:35:3:263. PMID 11894846. S2CID 31821726.
• Mongin AA (mart 2016). "Volume-regulated anion channel--a frenemy within the brain". Pflügers Archiv. 468 (3): 421–41. doi:10.1007/s00424-015-1765-6. PMC 4752865. PMID 26620797.
• Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (februar 2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID 10718198.
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• Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (april 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (oktobar 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Lehner B, Sanderson CM (juli 2004). "A protein interaction framework for human mRNA degradation". Genome Research. 14 (7): 1315–23. doi:10.1101/gr.2122004. PMC 442147. PMID 15231747.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (oktobar 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
• Kubota K, Kim JY, Sawada A, Tokimasa S, Fujisaki H, Matsuda-Hashii Y, Ozono K, Hara J (april 2004). "LRRC8 involved in B cell development belongs to a novel family of leucine-rich repeat proteins". FEBS Letters. 564 (1–2): 147–52. doi:10.1016/S0014-5793(04)00332-1. PMID 15094057.
• Smits G, Kajava AV (juli 2004). "LRRC8 extracellular domain is composed of 17 leucine-rich repeats". Molecular Immunology. 41 (5): 561–2. doi:10.1016/j.molimm.2004.04.001. PMID 15183935.
• Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Research. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (novembar 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.