Tomozin

Tomozin
Identifikatori
Aliasi	STXBP5
Vanjski ID-jevi	OMIM: 604586 MGI: 1926058 HomoloGene: 16402 GeneCards: STXBP5
Lokacija gena (čovjek)
Hrom.	Hromosom 6 (čovjek)
Kraj	147,390,476 bp
Lokacija gena (miš)
Hrom.	Hromosom 10 (miš)
Kraj	9,901,079 bp
Ontologija gena
Molekularna funkcija	• GO:0005097, GO:0005099, GO:0005100 GTPase activator activity; • syntaxin-1 binding; • syntaxin binding; • myosin II binding;
Ćelijska komponenta	• integral component of membrane; • acetylcholine-gated channel complex; • membrana; • Sinapsna vezikula; • ćelijska membrana; • sinapsa; • međućelijske veze; • cytoplasmic vesicle membrane; • GO:0016023 citoplazmatska vezikula; • citosol; • citoplazma; • Nervno-mišićna veza; • Schaffer collateral - CA1 synapse; • extrinsic component of presynaptic membrane; • presynaptic cytosol; • SNARE complex;
Biološki proces	• regulation of exocytosis; • protein transport; • positive regulation of exocytosis; • vesicle-mediated transport; • Egzocitoza; • regulation of protein secretion; • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity; • synaptic vesicle cycle;
	Izvori:Amigo / QuickGO
Ortolozi
	134957
	78808
	ENSG00000164506
	ENSMUSG00000019790
	Q5T5C0
	Q8K400
	NM_001127715; NM_139244; NM_001394409
	NM_001081344; NM_030191
	NP_001121187; NP_640337
	NP_001074813; NP_001394992; NP_001394993; NP_001394994
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

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]

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
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

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000164506 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000019790 - 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.

[pmid9620695-5] 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.

[pmid14767561-6] 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.

[entrez-7] "Entrez Gene: STXBP5 syntaxin binding protein 5 (tomosyn)".

[Hattendorf-8] 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.

[9] "Q5T5C0". SWISS-MODEL Repository.

[10] 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.

[11] 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.

[pmid12832401-12] 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.

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