AiPD: Autoinhibited Protein Database

O15498

Gene name	YKT6
Protein name	Synaptobrevin homolog YKT6
Names	EC 2.3.1.-
Species	Homo sapiens (Human)
KEGG Pathway	hsa:10652
EC number	2.3.1.-: Transferring groups other than amino-acyl groups
Protein Class

Descriptions

Most SNAREs are permanently anchored to membranes, but the dually lipidated SNARE Ykt6 is found both on intracellular membranes and in the cytoplasm. The SNARE core is autoinhibited by the N-terminal longin domain. <br>The dynamics of Ykt6 are believed to be governed by the reversible palmitoylation of the protein, which cycles Ykt6 between intracellular membranes and the cytoplasm. Palmitoylation of Ykt6 increases the partition coefficient of Ykt6 to membranes, thereby shifting some populations of the protein from the cytosol to cellular membranes. Palmitoylation-mediated membrane insertion will further shift the conformational equilibrium of Ykt6 to the open state. The specific membrane localization and the amount of membrane-associated Ykt6 are predicted to be affected by its reversible palmitoylation machinery in cells, as the majority of Ykt6 exists in the unpalmitoylated cytosolic form

Autoinhibitory domains (AIDs)

7-127 (Longin domain) SS

Target domain	138-198 (v-SNARE coiled-coil homology)
Relief mechanism	PTM
Assay

AID

7-127 (Longin domain)

Target domain

138-198 (v-SNARE coiled-coil homology)

Relief mechanism

PTM (Maybe palmitoylation of Cys196 in the C-terminal CCAIM motif)

Assay

Accessory elements

No accessory elements

References

Wen W et al. (2010) "Lipid-Induced conformational switch controls fusion activity of longin domain SNARE Ykt6", Molecular cell, 37, 383-95

Autoinhibited structure

Activated structure

4 structures for O15498

Entry ID	Method	Resolution	Chain	Position	Source
6J74	X-ray	321 A	C	1-198	PDB
6J7F	X-ray	288 A	C	1-195	PDB
6J7X	X-ray	275 A	C	1-198	PDB
AF-O15498-F1	Predicted				AlphaFoldDB

173 variants for O15498

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
TCGA novel	2	K>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs1562740487	2	K>Q		No	Ensembl
rs2096335005	2	K>R		No	TOPMed
rs957904298	3	L>P		No	TOPMed gnomAD
rs557185462	3	L>V		No	1000Genomes ExAC TOPMed gnomAD
rs2096335019	4	Y>H		No	gnomAD
rs757356224	5	S>R		No	ExAC gnomAD
rs1278676175	5	S>T		No	gnomAD
rs2096335034	6	L>F		No	Ensembl
rs778906573	7	S>G		No	ExAC TOPMed gnomAD
rs1460636013	8	V>G		No	gnomAD
rs141044177	9	L>F		No	1000Genomes ESP ExAC TOPMed gnomAD
rs141044177	9	L>V		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1444571069	10	Y>*		No	gnomAD
rs150272603	10	Y>C		No	1000Genomes ESP ExAC TOPMed gnomAD
rs1188872212	11	K>E	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA gnomAD
rs2096335075	12	G>A		No	TOPMed
rs2096335087	13	E>K		No	Ensembl
rs1260480876	14	A>S		No	TOPMed gnomAD
rs2096335094	15	K>E		No	Ensembl
rs755355202	16	V>M		No	ExAC gnomAD
rs748870	17	V>G		No	Ensembl
rs1486529076	18	L>Q		No	TOPMed gnomAD
rs2096335125	19	L>F		No	TOPMed
rs1562740562	20	K>R		No	Ensembl
rs866184383	21	A>S		No	Ensembl
rs774022853	22	A>P		No	ExAC TOPMed gnomAD
rs774022853	22	A>S		No	ExAC TOPMed gnomAD
rs2096335153	22	A>V		No	Ensembl
COSM3431616 rs374169220	23	Y>*	Variant assessed as Somatic; HIGH impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ESP ExAC TOPMed gnomAD
rs745479059	23	Y>C		No	ExAC TOPMed gnomAD
rs775371239	24	D>N	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA gnomAD
rs147946572	25	V>M		No	ESP ExAC TOPMed gnomAD
rs763866140	26	S>F		No	ExAC gnomAD
rs776602646	27	S>A		No	ExAC TOPMed gnomAD
rs2096335183	27	S>F		No	TOPMed
rs776602646	27	S>P		No	ExAC TOPMed gnomAD
rs370881857	28	F>L		No	ESP ExAC gnomAD
rs750502766	29	S>N		No	ExAC gnomAD
rs750502766	29	S>T		No	ExAC gnomAD
rs2128837798	32	Q>E		No	Ensembl
rs2096335201	33	R>K		No	Ensembl
rs2096335205	34	S>F		No	gnomAD
rs200537015	36	V>A		No	ESP ExAC TOPMed gnomAD
rs374571498	36	V>F		No	ESP ExAC TOPMed gnomAD
rs374571498 COSM3785698	36	V>I	pancreas [Cosmic]	No	cosmic curated ESP ExAC TOPMed gnomAD
rs2096338959	39	F>V		No	Ensembl
rs185914544	40	M>L		No	1000Genomes ExAC TOPMed gnomAD
rs1367857316	41	T>I		No	gnomAD
rs753008649	43	T>K		No	ExAC TOPMed gnomAD
rs753008649	43	T>M		No	ExAC TOPMed gnomAD
rs1265224121	44	S>G		No	TOPMed
rs1366763391	44	S>N		No	gnomAD
rs778414993	47	I>L		No	ExAC gnomAD
rs754467340	47	I>M		No	ExAC TOPMed gnomAD
rs1359419247	47	I>T		No	gnomAD
rs1267675271	49	E>Q		No	gnomAD
rs2096339012	49	E>V		No	TOPMed
rs199843184	50	R>C		No	1000Genomes ExAC TOPMed gnomAD
rs199843184	50	R>G		No	1000Genomes ExAC TOPMed gnomAD
rs368134203	50	R>H		No	ESP ExAC TOPMed gnomAD
rs141563755	52	S>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ESP ExAC NCI-TCGA TOPMed gnomAD
rs141563755	52	S>W		No	ESP ExAC TOPMed gnomAD
rs967331681	55	T>A		No	TOPMed gnomAD
rs1384514874	55	T>I		No	gnomAD
rs780632333	57	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA TOPMed
rs1286657456	60	K>E		No	gnomAD
rs769642918	60	K>R		No	ExAC TOPMed gnomAD
rs2096339073	62	Q>H		No	gnomAD
rs138273846	64	Y>C		No	ESP ExAC TOPMed gnomAD
rs1446402208	64	Y>H		No	gnomAD
rs138273846	64	Y>S		No	ESP ExAC TOPMed gnomAD
rs143932038	66	C>W		No	ESP ExAC TOPMed gnomAD
rs1160617543	67	H>Y		No	TOPMed gnomAD
COSM3768392 rs376107091	68	V>I	liver [Cosmic]	No	cosmic curated ExAC TOPMed gnomAD
rs372618652	69	Y>C		No	ESP ExAC gnomAD
rs1277939353	70	V>I		No	TOPMed gnomAD
rs761029409	71	R>Q		No	ExAC TOPMed gnomAD
rs775548288 COSM1233022	71	R>W	large_intestine [Cosmic]	No	cosmic curated ExAC TOPMed gnomAD
rs202098672	72	N>S		No	1000Genomes ExAC TOPMed gnomAD
rs1480300991 COSM223155	74	S>N	skin [Cosmic]	No	cosmic curated TOPMed gnomAD
rs754256887	82	D>V		No	ExAC gnomAD
rs2096340996	86	P>R		No	TOPMed
rs2096340987	86	P>T		No	Ensembl
rs765644782	88	R>P		No	ExAC TOPMed gnomAD
rs765644782	88	R>Q		No	ExAC TOPMed gnomAD
rs550011837	88	R>W		No	1000Genomes ExAC TOPMed gnomAD
rs754414111	89	V>L		No	ExAC gnomAD
rs2096341025	90	A>T		No	TOPMed
rs767101133	90	A>V		No	ExAC gnomAD
rs752296251	94	L>Q		No	ExAC gnomAD
rs2096341055	95	E>A		No	gnomAD
rs571774649	95	E>D		No	1000Genomes ExAC TOPMed gnomAD
rs2128839394	96	K>*		No	Ensembl
rs1354516091	99	D>E		No	TOPMed gnomAD
rs1429614754	101	F>C		No	gnomAD
TCGA novel	101	F>L	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs143284758	102	S>C		No	ESP ExAC TOPMed gnomAD
rs773570225	102	S>P		No	ExAC gnomAD
rs773570225	102	S>T		No	ExAC gnomAD
rs1323377543	105	V>A		No	gnomAD
rs1438883980 COSM3431617	106	D>N	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated NCI-TCGA gnomAD
rs1473695508	107	R>S		No	TOPMed gnomAD
rs1014962983	110	W>*		No	TOPMed gnomAD
rs755707761	110	W>R		No	ExAC TOPMed gnomAD
rs1014962983	110	W>S		No	TOPMed gnomAD
rs1583647564 COSM1089929	111	P>S	Variant assessed as Somatic; MODERATE impact. endometrium [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated Ensembl
rs1583647572	112	V>G		No	Ensembl
rs1226032982	113	G>A		No	gnomAD
rs2096341939	113	G>R		No	TOPMed
rs1299696747	114	S>A		No	gnomAD
rs112426773	114	S>C		No	Ensembl
rs1583647600	115	P>S		No	Ensembl
TCGA novel	118	I>M	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs963366243	118	I>V		No	TOPMed
rs1583647615	119	H>P		No	Ensembl
rs1209010661	120	Y>F		No	gnomAD
rs2096341973	121	P>L		No	gnomAD
rs2096341975	122	A>V		No	Ensembl
rs144641826	123	L>V		No	1000Genomes ExAC gnomAD
rs570507763	124	D>E		No	1000Genomes ExAC TOPMed gnomAD
rs2096341981	124	D>N		No	Ensembl
rs201188604	126	H>L		No	1000Genomes
rs1321161946	126	H>Q		No	TOPMed gnomAD
TCGA novel	129	R>I	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA
rs2096342001	129	R>S		No	TOPMed
rs1246829336	130	Y>H		No	gnomAD
rs959201807	131	Q>*		No	Ensembl
COSM4741858 rs753469894	134	R>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic ExAC NCI-TCGA gnomAD
rs2096342920	134	R>Q		No	TOPMed
TCGA novel	135	E>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA
rs761553542	136	A>T		No	ExAC gnomAD
rs764904707	136	A>V	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs1266027342	137	D>H		No	TOPMed
rs1019274884	139	M>T		No	TOPMed
rs1206624926	139	M>V		No	TOPMed
rs750242578	140	T>I		No	ExAC TOPMed gnomAD
rs780133803 COSM172290	145	E>K	Variant assessed as Somatic; MODERATE impact. large_intestine [NCI-TCGA, Cosmic]	No	NCI-TCGA Cosmic cosmic curated ExAC NCI-TCGA TOPMed gnomAD
rs2096342976	148	E>G		No	Ensembl
rs772944817	150	K>R		No	ExAC TOPMed gnomAD
rs772944817	150	K>T		No	ExAC TOPMed gnomAD
rs2096342982	151	I>V		No	TOPMed
rs762715210	155	N>S		No	ExAC TOPMed gnomAD
rs2096346244	156	T>S		No	Ensembl
rs774293163	158	E>G		No	ExAC gnomAD
rs1488272305	158	E>K		No	gnomAD
rs767550148	159	S>A		No	ExAC gnomAD
rs752644714	160	L>V		No	ExAC TOPMed gnomAD
rs756189723	162	E>G		No	ExAC gnomAD
COSM1089930	163	R>*	Variant assessed as Somatic; HIGH impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs2096346263	163	R>G		No	Ensembl
rs764130626	163	R>Q	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs1170871324	164	G>A		No	gnomAD
rs754045609	165	E>G		No	ExAC gnomAD
rs2096346284	171	V>M		No	Ensembl
rs866811977	172	S>F		No	Ensembl
rs2096346303	175	E>K		No	Ensembl
rs916832961	176	V>L		No	TOPMed gnomAD
rs2128840745	180	Q>*		No	Ensembl
COSM1313106	181	S>C	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1363641420	182	K>*		No	gnomAD
rs2096346323	183	A>V		No	TOPMed
COSM1089931	186	K>T	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	NCI-TCGA Cosmic
rs1583650537	187	T>P		No	Ensembl
rs747509605	189	R>G		No	ExAC TOPMed gnomAD
rs141713796	189	R>Q		No	ESP TOPMed gnomAD
rs747509605	189	R>W	Variant assessed as Somatic; MODERATE impact. [NCI-TCGA]	No	ExAC NCI-TCGA TOPMed gnomAD
rs1183379380	190	K>E		No	gnomAD
rs2096347668	193	S>A		No	Ensembl
rs2096347669	194	C>R		No	Ensembl
rs774116833	194	C>W		No	ExAC TOPMed gnomAD
rs1174763015	196	A>V		No	gnomAD
rs1359023676	197	I>V		No	gnomAD

No associated diseases with O15498

3 regional properties for O15498

Type	Name	Position	InterPro Accession
domain	Longin domain	4 - 130	IPR010908
domain	v-SNARE, coiled-coil homology domain	136 - 198	IPR042855
domain	YKT6, SNARE motif	136 - 195	IPR045848

Functions

		Description
EC Number	2.3.1.-	Transferring groups other than amino-acyl groups
Subcellular Localization	Cytoplasm, cytosol Cytoplasmic vesicle membrane; Lipid-anchor; Cytoplasmic side Golgi apparatus membrane; Lipid-anchor; Cytoplasmic side	Probably cycles through vesicles between Golgi and endosomes
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

15 GO annotations of cellular component

Name	Definition
apical dendrite	A dendrite that emerges near the apical pole of a neuron. In bipolar neurons, apical dendrites are located on the opposite side of the soma from the axon.
basal dendrite	A dendrite that emerges near the basal pole of a neuron. In bipolar neurons, basal dendrites are either on the same side of the soma as the axon, or project toward the axon.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytoplasmic vesicle membrane	The lipid bilayer surrounding a cytoplasmic vesicle.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
endoplasmic reticulum	The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
endoplasmic reticulum-Golgi intermediate compartment membrane	The lipid bilayer surrounding any of the compartments of the endoplasmic reticulum (ER)-Golgi intermediate compartment system.
endosome	A vacuole to which materials ingested by endocytosis are delivered.
Golgi apparatus	A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
Golgi membrane	The lipid bilayer surrounding any of the compartments of the Golgi apparatus.
mitochondrion	A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
neuronal cell body	The portion of a neuron that includes the nucleus, but excludes cell projections such as axons and dendrites.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
SNARE complex	A protein complex involved in membrane fusion; a stable ternary complex consisting of a four-helix bundle, usually formed from one R-SNARE and three Q-SNAREs with an ionic layer sandwiched between hydrophobic layers. One well-characterized example is the neuronal SNARE complex formed of synaptobrevin 2, syntaxin 1a, and SNAP-25.
transport vesicle	Any of the vesicles of the constitutive secretory pathway, which carry cargo from the endoplasmic reticulum to the Golgi, between Golgi cisternae, from the Golgi to the ER (retrograde transport) or to destinations within or outside the cell.

3 GO annotations of molecular function

Name	Definition
cadherin binding	Binding to cadherin, a type I membrane protein involved in cell adhesion.
protein-cysteine S-palmitoyltransferase activity	Catalysis of the transfer of a palmitoyl (systematic name, hexadecanoyl) group to a sulfur atom on the cysteine of a protein molecule, in the reaction hexadecanoyl-CoA + L-cysteinyl- = CoA + S-hexadecanoyl-L-cysteinyl-.
SNAP receptor activity	Acting as a marker to identify a membrane and interacting selectively with one or more SNAREs on another membrane to mediate membrane fusion.

5 GO annotations of biological process

Name	Definition
endoplasmic reticulum to Golgi vesicle-mediated transport	The directed movement of substances from the endoplasmic reticulum (ER) to the Golgi, mediated by COP II vesicles. Small COP II coated vesicles form from the ER and then fuse directly with the cis-Golgi. Larger structures are transported along microtubules to the cis-Golgi.
protein transport	The directed movement of proteins into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
retrograde transport, endosome to Golgi	The directed movement of membrane-bounded vesicles from endosomes back to the trans-Golgi network where they are recycled for further rounds of transport.
vesicle docking involved in exocytosis	The initial attachment of a vesicle membrane to a target membrane, mediated by proteins protruding from the membrane of the vesicle and the target membrane, that contributes to exocytosis.
vesicle targeting	The process in which vesicles are directed to specific destination membranes. Targeting involves coordinated interactions among cytoskeletal elements (microtubules or actin filaments), motor proteins, molecules at the vesicle membrane and target membrane surfaces, and vesicle cargo.

8 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P36015	YKT6	Synaptobrevin homolog YKT6	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	EV
Q3T000	YKT6	Synaptobrevin homolog YKT6	Bos taurus (Bovine)	SS
Q9CQW1	Ykt6	Synaptobrevin homolog YKT6	Mus musculus (Mouse)	SS
Q5EGY4	Ykt6	Synaptobrevin homolog YKT6	Rattus norvegicus (Rat)	EV
Q9LVM9	YKT62	VAMP-like protein YKT62	Arabidopsis thaliana (Mouse-ear cress)	PR
Q9ZRD6	YKT61	VAMP-like protein YKT61	Arabidopsis thaliana (Mouse-ear cress)	SS
Q6P816	ykt6	Synaptobrevin homolog YKT6	Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)	SS
Q7ZUN8	ykt6	Synaptobrevin homolog YKT6	Danio rerio (Zebrafish) (Brachydanio rerio)	SS

10	20	30	40	50	60
MKLYSLSVLY	KGEAKVVLLK	AAYDVSSFSF	FQRSSVQEFM	TFTSQLIVER	SSKGTRASVK
70	80	90	100	110	120
EQDYLCHVYV	RNDSLAGVVI	ADNEYPSRVA	FTLLEKVLDE	FSKQVDRIDW	PVGSPATIHY
130	140	150	160	170	180
PALDGHLSRY	QNPREADPMT	KVQAELDETK	IILHNTMESL	LERGEKLDDL	VSKSEVLGTQ
190
SKAFYKTARK	QNSCCAIM