UNC93B1

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

UNC93B1
Identifikatori
Aliasi	UNC93B1
Vanjski ID-jevi	OMIM: 608204 MGI: 1859307 HomoloGene: 41325 GeneCards: UNC93B1
Lokacija gena (čovjek) Hrom. Hromosom 11 (čovjek)[1] Bend 11q13.2 Početak 67,991,100 bp[1] Kraj 68,004,982 bp[1]
Lokacija gena (miš) Hrom. Hromosom 19 (miš)[2] Bend 19|19 A Početak 3,985,186 bp[2] Kraj 3,999,340 bp[2]
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
Vrste	Čovjek	Miš
Entrez	81622	54445
Ensembl	ENSG00000110057	ENSMUSG00000036908
UniProt	Q9H1C4	Q8VCW4
RefSeq (mRNK)	NM_030930	NM_001161428 NM_019449
RefSeq (bjelančevina)	NP_112192	NP_001154900 NP_062322
Lokacija (UCSC)	Chr 11: 67.99 – 68 Mb	Chr 19: 3.99 – 4 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

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

1. GRCh38: Ensembl release 89: ENSG00000110057 - Ensembl, maj 2017
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.
5. "Entrez Gene: UNC93B1 unc-93 homolog B1 (C. elegans)".
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.
7. "UniProt, Q9H1C4". Pristupljeno 28. 8. 2021.
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.
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.
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.

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.