UNC93B1

UNC93B1
Identifikatori
Aliasi	UNC93B1
Vanjski ID-jevi	OMIM: 608204 MGI: 1859307 HomoloGene: 41325 GeneCards: UNC93B1
Lokacija gena (čovjek)
Hrom.	Hromosom 11 (čovjek)
Kraj	68,004,982 bp
Lokacija gena (miš)
Hrom.	Hromosom 19 (miš)
Kraj	3,999,340 bp
Ontologija gena
Molekularna funkcija	• Toll-like receptor binding;
Ćelijska komponenta	• integral component of membrane; • early phagosome; • Golđijeva membrana; • endozom; • Lizozom; • phagocytic vesicle; • endoplasmic reticulum membrane; • Endoplazmatski retikulum; • membrana; • GO:0016023 citoplazmatska vezikula;
Biološki proces	• toll-like receptor 9 signaling pathway; • intracellular protein transport; • toll-like receptor 3 signaling pathway; • adaptive immune response; • defense response to virus; • toll-like receptor 7 signaling pathway; • toll-like receptor signaling pathway; • immune system process; • Urođeni imunski sistem;
	Izvori:Amigo / QuickGO
Ortolozi
	81622
	54445
	ENSG00000110057
	ENSMUSG00000036908
	Q9H1C4
	Q8VCW4
	NM_030930
	NM_001161428; NM_019449
	NP_112192
	NP_001154900; NP_062322
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Unc-93 homolog B1 (C. elegans), znan i kao UNC93B1, jest protein koji je kod ljudi kodiran genom UNC93B1.^[5]^[6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 597 aminokiselina, а molekulska težina 66.631 Da.^[7]

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
MEAEPPLYPM	AGAAGPQGDE	DLLGVPDGPE	APLDELVGAY	PNYNEEEEER
RYYRRKRLGV	LKNVLAASAG	GMLTYGVYLG	LLQMQLILHY	DETYREVKYG
NMGLPDIDSK	MLMGINVTPI	AALLYTPVLI	RFFGTKWMMF	LAVGIYALFV
STNYWERYYT	LVPSAVALGM	AIVPLWASMG	NYITRMAQKY	HEYSHYKEQD
GQGMKQRPPR	GSHAPYLLVF	QAIFYSFFHL	SFACAQLPMI	YFLNHYLYDL
NHTLYNVQSC	GTNSHGILSG	FNKTVLRTLP	RSGNLIVVES	VLMAVAFLAM
LLVLGLCGAA	YRPTEEIDLR	SVGWGNIFQL	PFKHVRDYRL	RHLVPFFIYS
GFEVLFACTG	IALGYGVCSV	GLERLAYLLV	AYSLGASAAS	LLGLLGLWLP
RPVPLVAGAG	VHLLLTFILF	FWAPVPRVLQ	HSWILYVAAA	LWGVGSALNK
TGLSTLLGIL	YEDKERQDFI	FTIYHWWQAV	AIFTVYLGSS	LHMKAKLAVL
LVTLVAAAVS	YLRMEQKLRR	GVAPRQPRIP	RPQHKVRGYR	YLEEDNSDES
DAEGEHGDGA	EEEAPPAGPR	PGPEPAGLGR	RPCPYEQAQG	GDGPEEQ

Funkcija

Ovaj gen kodira protein sličan proteinu Caenorhabditis elegans unc93. Protein Unc93 uključen je u regulaciju ili koordinaciju mišićne kontrakcije te oble gliste.^[5]

Molekulska biologija

Gen se nalazi na dugom kraku hromosoma 11 (11q13) na minus (Crick) sekvenci^[6] i prvi put je identifikovan 2002.^[6] Ovaj protein je intrinzični membranski protein koji pokriva membranu dvanaest puta. Nalazi se u endoplazmatskom retikulumu i visoko je konzerviran.

Klinički značaj

Protein Unc93B1 uključen je u urođeni imunski odgovor. Defekti proteina predisponiraju preosjetljivost na infekcije herpes simplex virus i mišjeg citomegalovirusa.^[8] Mehanizam nije jasan, ali poznato je da Unc93B1 stupa u interakciju sa toll-likim receptorima TLR3, TLR7 i TLR9 i čini se da je uključen u promet ovih receptora unutar ćelije.^[9]^[10] Mutacije u ovom genu dovode do selektivnog oštećenja interferona alfa/beta izazvanog dsRNK i proizvodnje lambda interferona 1.

Pokazano je da unutarćelijski toll-liki receptori stupaju u interakciju s UNC93B u splenocitima i dendritskim ćelijama iz koštane srži. TLR3 i TLR9 vežu se za UNC93B preko svojih transmembranskih domena. Uvođenje tačkaste mutacije H412R (histidin u arginin) na aminokiselini 412: jedna baza se tzranslocira – adenozin u guanin na bazi 1235), a u UNC93B ukida ovu interakciju.

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000110057 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000036908 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: UNC93B1 unc-93 homolog B1 (C. elegans)".
^ ^a ^b ^c Kashuba VI, Protopopov AI, Kvasha SM, Gizatullin RZ, Wahlestedt C, Kisselev LL, Klein G, Zabarovsky ER (januar 2002). "hUNC93B1: a novel human gene representing a new gene family and encoding an unc-93-like protein". Gene. 283 (1–2): 209–17. doi:10.1016/S0378-1119(01)00856-3. PMID 11867227.
^ "UniProt, Q9H1C4". Pristupljeno 28. 8. 2021.
^ Casrouge A, Zhang SY, Eidenschenk C, Jouanguy E, Puel A, Yang K, Alcais A, Picard C, Mahfoufi N, Nicolas N, Lorenzo L, Plancoulaine S, Sénéchal B, Geissmann F, Tabeta K, Hoebe K, Du X, Miller RL, Héron B, Mignot C, de Villemeur TB, Lebon P, Dulac O, Rozenberg F, Beutler B, Tardieu M, Abel L, Casanova JL (oktobar 2006). "Herpes simplex virus encephalitis in human UNC-93B deficiency". Science. 314 (5797): 308–12. doi:10.1126/science.1128346. PMID 16973841. S2CID 12501759.
^ Tabeta K, Hoebe K, Janssen EM, Du X, Georgel P, Crozat K, Mudd S, Mann N, Sovath S, Goode J, Shamel L, Herskovits AA, Portnoy DA, Cooke M, Tarantino LM, Wiltshire T, Steinberg BE, Grinstein S, Beutler B (februar 2006). "The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9". Nat. Immunol. 7 (2): 156–64. doi:10.1038/ni1297. PMID 16415873. S2CID 33401155.
^ Kim YM, Brinkmann MM, Paquet ME, Ploegh HL (mart 2008). "UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes". Nature. 452 (7184): 234–8. doi:10.1038/nature06726. PMID 18305481. S2CID 4397023.

Dopunska literatura

Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID 8619474.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Yu W, Andersson B, Worley KC, et al. (1997). "Large-Scale Concatenation cDNA Sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
Sanger Centre, The; Washington University Genome Sequencing Cente, The (1999). "Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. doi:10.1101/gr.8.11.1097. PMID 9847074.
Kashuba VI, Protopopov AI, Kvasha SM, et al. (2002). "hUNC93B1: a novel human gene representing a new gene family and encoding an unc-93-like protein". Gene. 283 (1–2): 209–17. doi:10.1016/S0378-1119(01)00856-3. PMID 11867227.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Arnlöv J, Sundström J, Lind L, et al. (2006). "hUNC-93B1, a novel gene mainly expressed in the heart, is related to left ventricular diastolic function, heart failure morbidity and mortality in elderly men". Eur. J. Heart Fail. 7 (6): 958–65. doi:10.1016/j.ejheart.2004.06.009. PMID 16111919. S2CID 22339419.
Taylor TD, Noguchi H, Totoki Y, et al. (2006). "Human chromosome 11 DNA sequence and analysis including novel gene identification". Nature. 440 (7083): 497–500. doi:10.1038/nature04632. PMID 16554811.
Casrouge A, Zhang SY, Eidenschenk C, et al. (2006). "Herpes simplex virus encephalitis in human UNC-93B deficiency". Science. 314 (5797): 308–12. doi:10.1126/science.1128346. PMID 16973841. S2CID 12501759.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000110057 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000036908 - 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.

[entrez-5] "Entrez Gene: UNC93B1 unc-93 homolog B1 (C. elegans)".

[pmid11867227-6] Kashuba VI, Protopopov AI, Kvasha SM, Gizatullin RZ, Wahlestedt C, Kisselev LL, Klein G, Zabarovsky ER (januar 2002). "hUNC93B1: a novel human gene representing a new gene family and encoding an unc-93-like protein". Gene. 283 (1–2): 209–17. doi:10.1016/S0378-1119(01)00856-3. PMID 11867227.

[UniProt-7] "UniProt, Q9H1C4". Pristupljeno 28. 8. 2021.

[pmid16973841-8] Casrouge A, Zhang SY, Eidenschenk C, Jouanguy E, Puel A, Yang K, Alcais A, Picard C, Mahfoufi N, Nicolas N, Lorenzo L, Plancoulaine S, Sénéchal B, Geissmann F, Tabeta K, Hoebe K, Du X, Miller RL, Héron B, Mignot C, de Villemeur TB, Lebon P, Dulac O, Rozenberg F, Beutler B, Tardieu M, Abel L, Casanova JL (oktobar 2006). "Herpes simplex virus encephalitis in human UNC-93B deficiency". Science. 314 (5797): 308–12. doi:10.1126/science.1128346. PMID 16973841. S2CID 12501759.

[pmid16415873-9] Tabeta K, Hoebe K, Janssen EM, Du X, Georgel P, Crozat K, Mudd S, Mann N, Sovath S, Goode J, Shamel L, Herskovits AA, Portnoy DA, Cooke M, Tarantino LM, Wiltshire T, Steinberg BE, Grinstein S, Beutler B (februar 2006). "The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9". Nat. Immunol. 7 (2): 156–64. doi:10.1038/ni1297. PMID 16415873. S2CID 33401155.

[pmid18305481-10] Kim YM, Brinkmann MM, Paquet ME, Ploegh HL (mart 2008). "UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes". Nature. 452 (7184): 234–8. doi:10.1038/nature06726. PMID 18305481. S2CID 4397023.

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