Tomozin
Sintaksin-vezujući protein 5 jest protein koji je kod ljudi kodiran genom STXBP5 sa hromosoma 6. Također je poznat kao tomozin, po japanskom 友 = "prijatelj", zbog svoje uloge vezujućeg proteina.[5][6][7]
Aminokiselinska sekvenca
Dužina polipeptidnog lanca je 1.151 aminokiselina, a molekulska težina 127.573 Da.[7]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MRKFNIRKVL | DGLTAGSSSA | SQQQQQQHPP | GNREPEIQET | LQSEHFQLCK | ||||
| TVRHGFPYQP | SALAFDPVQK | ILAVGTQTGA | LRLFGRPGVE | CYCQHDSGAA | ||||
| VIQLQFLINE | GALVSALADD | TLHLWNLRQK | RPAILHSLKF | CRERVTFCHL | ||||
| PFQSKWLYVG | TERGNIHIVN | VESFTLSGYV | IMWNKAIELS | SKSHPGPVVH | ||||
| ISDNPMDEGK | LLIGFESGTV | VLWDLKSKKA | DYRYTYDEAI | HSVAWHHEGK | ||||
| QFICSHSDGT | LTIWNVRSPA | KPVQTITPHG | KQLKDGKKPE | PCKPILKVEF | ||||
| KTTRSGEPFI | ILSGGLSYDT | VGRRPCLTVM | HGKSTAVLEM | DYSIVDFLTL | ||||
| CETPYPNDFQ | EPYAVVVLLE | KDLVLIDLAQ | NGYPIFENPY | PLSIHESPVT | ||||
| CCEYFADCPV | DLIPALYSVG | ARQKRQGYSK | KEWPINGGNW | GLGAQSYPEI | ||||
| IITGHADGSV | KFWDASAITL | QVLYKLKTSK | VFEKSRNKDD | RPNTDIVDED | ||||
| PYAIQIISWC | PESRMLCIAG | VSAHVIIYRF | SKQEVITEVI | PMLEVRLLYE | ||||
| INDVETPEGE | QPPPLPTPVG | GSNPQPIPPQ | SHPSTSSSSS | DGLRDNVPCL | ||||
| KVKNSPLKQS | PGYQTELVIQ | LVWVGGEPPQ | QITSLAVNSS | YGLVVFGNCN | ||||
| GIAMVDYLQK | AVLLNLGTIE | LYGSNDPYRR | EPRSPRKSRQ | PSGAGLCDIS | ||||
| EGTVVPEDRC | KSPTSGSSSP | HNSDDEQKMN | NFIEKVKTKS | RKFSKMVAND | ||||
| IAKMSRKLSL | PTDLKPDLDV | KDNSFSRSRS | SSVTSIDKES | REAISALHFC | ||||
| ETFTRKTDSS | PSPCLWVGTT | LGTVLVIALN | LPPGGEQRLL | QPVIVSPSGT | ||||
| ILRLKGAILR | MAFLDTTGCL | IPPAYEPWRE | HNVPEEKDEK | EKLKKRRPVS | ||||
| VSPSSSQEIS | ENQYAVICSE | KQAKVISLPT | QNCAYKQNIT | ETSFVLRGDI | ||||
| VALSNSICLA | CFCANGHIMT | FSLPSLRPLL | DVYYLPLTNM | RIARTFCFTN | ||||
| NGQALYLVSP | TEIQRLTYSQ | ETCENLQEML | GELFTPVETP | EAPNRGFFKG | ||||
| LFGGGAQSLD | REELFGESSS | GKASRSLAQH | IPGPGGIEGV | KGAASGVVGE | ||||
| LARARLALDE | RGQKLGDLEE | RTAAMLSSAE | SFSKHAHEIM | LKYKDKKWYQ | ||||
| F |
Struktura
Prvobitno su identificirane dva funkcionalna domena, uključujući jedan koji se veže za sintaksin, ali je nedavna kristalizacija homologa kvasca Sro7 otkrila da tomozin vjerovatno ima tri funkcionalna domena: jedan WD40 domen i jedan domen koji se veže za sintaksin, kao što je prethodno prepoznato, ali i drugi WD40 domen. Studija je također sugerirala da tomozinski 'sintaksin vezujući domen' nije razlog zašto tomozin inhibira oslobađanje neurotransmitera, kao što je prvobitno predloženo.[8] Struktura zasnovana na Sro7 data je na SWISS-MODEL-u, koji uključuje WD40 domene, ali ne i većinu domena upredene zavojnice koji veže sintaksin vidljiv u infokutiji.[9]
Funkcija
Sintaksin 1 je komponenta 7S i 20S SNARE kompleksa koji su uključeni u preradu i fuziju sinapsnih vezikula sa presinapsnom plazmamembranom. Ovaj gen kodira protein koji se vezuje za sintaksin 1. Kod pacova, sličan protein disocira sintaksin 1 od kompleksa Munc18/n-Sec1/rbSec1, da bi se formirao 10S kompleks, intermedijer koji se može konvertovati u 7S SNARE kompleks. Stoga se smatra da je ovaj protein uključen u oslobađanje neurotransmitera, stimulirajući formiranje SNARE kompleksa. Identificirane su alternativno prerađene varijante transkripta, ali njihova biološka valjanost nije utvrđena.[7]
Poziciono kloniranje sugerira da tomozin može inhibirati lučenje neurotransmitera u neuronima Caenorhabditis elegans.[10] Ova hipoteza je testirana i potvrđena, pokazujući da tomozin specifično inhibira primanje sinapsnih vezikula – biohemijski korak koji neposredno prethodi fuziji vezikula i oslobađanju neurotransmitera.[11]
Interakcije
Pokazalo se da STXBP5 ima interakcije sa STX4[12] i STX1A.[5][12]
Reference
- ^ a b c GRCh38: Ensembl release 89: ENSG00000164506 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000019790 - 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 Fujita Y, Shirataki H, Sakisaka T, Asakura T, Ohya T, Kotani H, Yokoyama S, Nishioka H, Matsuura Y, Mizoguchi A, Scheller RH, Takai Y (Jun 1998). "Tomosyn: a syntaxin-1-binding protein that forms a novel complex in the neurotransmitter release process". Neuron. 20 (5): 905–15. doi:10.1016/S0896-6273(00)80472-9. PMID 9620695. S2CID 12597505.
- ^ Katoh M, Katoh M (Feb 2004). "Identification and characterization of human LLGL4 gene and mouse Llgl4 gene in silico". Int. J. Oncol. 24 (3): 737–42. doi:10.3892/ijo.24.3.737. PMID 14767561.
- ^ a b c "Entrez Gene: STXBP5 syntaxin binding protein 5 (tomosyn)".
- ^ Hattendorf DA, Andreeva A, Gangar A, Brennwald PJ, Weis WI (mart 2007). "Structure of the yeast polarity protein Sro7 reveals a SNARE regulatory mechanism". Nature. 446 (7135): 567–71. Bibcode:2007Natur.446..567H. doi:10.1038/nature05635. PMID 17392788. S2CID 4399611.
- ^ "Q5T5C0". SWISS-MODEL Repository.
- ^ Dybbs M, Ngai J, Kaplan JM (juli 2005). "Using microarrays to facilitate positional cloning: identification of tomosyn as an inhibitor of neurosecretion". PLOS Genet. 1 (1): 6–16. doi:10.1371/journal.pgen.0010002. PMC 1183521. PMID 16103915.
- ^ Gracheva EO, Burdina AO, Holgado AM, et al. (juli 2006). "Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans". PLOS Biol. 4 (8): e261. doi:10.1371/journal.pbio.0040261. PMC 1514790. PMID 16895441.
- ^ a b Widberg CH, Bryant NJ, Girotti M, Rea S, James DE (Sep 2003). "Tomosyn interacts with the t-SNAREs syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation". J. Biol. Chem. 278 (37): 35093–101. doi:10.1074/jbc.M304261200. PMID 12832401.
Dopunska literatura
- Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (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.
- Widberg CH, Bryant NJ, Girotti M, Rea S, James DE (2003). "Tomosyn interacts with the t-SNAREs syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation". J. Biol. Chem. 278 (37): 35093–101. doi:10.1074/jbc.M304261200. PMID 12832401.
- Yokoyama S, Shirataki H, Sakisaka T, Takai Y (1999). "Three splicing variants of tomosyn and identification of their syntaxin-binding region". Biochem. Biophys. Res. Commun. 256 (1): 218–22. doi:10.1006/bbrc.1999.0300. PMID 10066450.
Vanjski linkovi
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