VAMP2_HUMAN
ID VAMP2_HUMAN Reviewed; 116 AA.
AC P63027; P19065; Q9BUC2;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 3.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Vesicle-associated membrane protein 2 {ECO:0000305};
DE Short=VAMP-2;
DE AltName: Full=Synaptobrevin-2;
GN Name=VAMP2 {ECO:0000312|HGNC:HGNC:12643}; Synonyms=SYB2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1976629; DOI=10.1016/s0021-9258(17)44898-8;
RA Archer B.T. III, Oezcelik T., Jahn R., Francke U., Suedhof T.C.;
RT "Structures and chromosomal localizations of two human genes encoding
RT synaptobrevins 1 and 2.";
RL J. Biol. Chem. 265:17267-17273(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Peripheral blood;
RA Nabokina S.M., Lazo P.A., Mollinedo F.;
RT "Expression of VAMP genes in human neutrophils.";
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RA Taruscio D., Zoraqi K.G., Falbo V.;
RT "Genomic structure of human SYB2 gene.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neuroblastoma, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=8760387; DOI=10.1042/bj3170945;
RA Jagadish M.N., Fernandez C.S., Hewish D.R., Macaulay S.L., Gough K.H.,
RA Grusovin J., Verkuylen A., Cosgrove L., Alafaci A., Frenkel M.J.,
RA Ward C.W.;
RT "Insulin-responsive tissues contain the core complex protein SNAP-25
RT (synaptosomal-associated protein 25) A and B isoforms in addition to
RT syntaxin 4 and synaptobrevins 1 and 2.";
RL Biochem. J. 317:945-954(1996).
RN [8]
RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION) BY C.BOTULINUM NEUROTOXIN TYPE B
RP AND BY C.TETANI TETANUS TOXIN.
RX PubMed=7803399; DOI=10.1021/bi00255a017;
RA Foran P., Shone C.C., Dolly J.O.;
RT "Differences in the protease activities of tetanus and botulinum B toxins
RT revealed by the cleavage of vesicle-associated membrane protein and various
RT sized fragments.";
RL Biochemistry 33:15365-15374(1994).
RN [9]
RP TOPOLOGY.
RX PubMed=7835332; DOI=10.1002/j.1460-2075.1995.tb06994.x;
RA Kutay U., Ahnert-Hilger G., Hartmann E., Wiedenmann B., Rapoport T.A.;
RT "Transport route for synaptobrevin via a novel pathway of insertion into
RT the endoplasmic reticulum membrane.";
RL EMBO J. 14:217-223(1995).
RN [10]
RP INTERACTION WITH WDFY2; PRKCZ AND PRKCI, COMPLEX FORMATION WITH WDFY2 AND
RP PRKCZ, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS OF SER-28;
RP SER-61; SER-75 AND SER-80.
RX PubMed=17313651; DOI=10.1111/j.1742-4658.2007.05702.x;
RA Fritzius T., Frey A.D., Schweneker M., Mayer D., Moelling K.;
RT "WD-repeat-propeller-FYVE protein, ProF, binds VAMP2 and protein kinase
RT Czeta.";
RL FEBS J. 274:1552-1566(2007).
RN [11]
RP RETRACTED PAPER.
RX PubMed=10932255; DOI=10.1038/77997;
RA Hanson M.A., Stevens R.C.;
RT "Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type
RT B at 2.0 A resolution.";
RL Nat. Struct. Biol. 7:687-692(2000).
RN [12]
RP RETRACTION NOTICE OF PUBMED:10932255.
RX PubMed=19578378; DOI=10.1038/nsmb0709-795;
RA Hanson M.A., Stevens R.C.;
RT "Retraction: Cocrystal structure of synaptobrevin-II bound to botulinum
RT neurotoxin type B at 2.0 A resolution.";
RL Nat. Struct. Mol. Biol. 16:795-795(2009).
RN [13]
RP INTERACTION WITH ALPHA-SYNUCLEIN/SNCA.
RX PubMed=20798282; DOI=10.1126/science.1195227;
RA Burre J., Sharma M., Tsetsenis T., Buchman V., Etherton M.R., Suedhof T.C.;
RT "Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro.";
RL Science 329:1663-1667(2010).
RN [14]
RP INTERACTION WITH PICALM.
RX PubMed=22118466; DOI=10.1016/j.cell.2011.10.038;
RA Miller S.E., Sahlender D.A., Graham S.C., Honing S., Robinson M.S.,
RA Peden A.A., Owen D.J.;
RT "The molecular basis for the endocytosis of small R-SNAREs by the clathrin
RT adaptor CALM.";
RL Cell 147:1118-1131(2011).
RN [15]
RP INTERACTION WITH PICALM.
RX PubMed=21808019; DOI=10.1073/pnas.1107067108;
RA Koo S.J., Markovic S., Puchkov D., Mahrenholz C.C., Beceren-Braun F.,
RA Maritzen T., Dernedde J., Volkmer R., Oschkinat H., Haucke V.;
RT "SNARE motif-mediated sorting of synaptobrevin by the endocytic adaptors
RT clathrin assembly lymphoid myeloid leukemia (CALM) and AP180 at synapses.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:13540-13545(2011).
RN [16]
RP PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION) BY C.BOTULINUM NEUROTOXIN TYPES
RP B; D AND F.
RX PubMed=22289120; DOI=10.1111/j.1348-0421.2012.00434.x;
RA Yamamoto H., Ida T., Tsutsuki H., Mori M., Matsumoto T., Kohda T.,
RA Mukamoto M., Goshima N., Kozaki S., Ihara H.;
RT "Specificity of botulinum protease for human VAMP family proteins.";
RL Microbiol. Immunol. 56:245-253(2012).
RN [17] {ECO:0007744|PDB:3FIE, ECO:0007744|PDB:3FII}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 25-57 IN COMPLEX WITH C.BOTULINUM
RP NEUROTOXIN F LIGHT CHAIN, PROTEOLYTIC CLEAVAGE (MICROBIAL INFECTION) BY
RP C.BOTULINUM NEUROTOXIN TYPE X, AND MUTAGENESIS OF GLU-41; VAL-50; VAL-53
RP AND 53-VAL-LEU-54.
RX PubMed=19543288; DOI=10.1038/nsmb.1626;
RA Agarwal R., Schmidt J.J., Stafford R.G., Swaminathan S.;
RT "Mode of VAMP substrate recognition and inhibition of Clostridium botulinum
RT neurotoxin F.";
RL Nat. Struct. Mol. Biol. 16:789-794(2009).
RN [18]
RP VARIANTS NEDHAHM VAL-43 DEL; ILE-45 DEL; PRO-75; SER-77 AND ALA-78,
RP CHARACTERIZATION OF VARIANTS NEDHAHM PRO-75 AND ALA-78, AND FUNCTION.
RX PubMed=30929742; DOI=10.1016/j.ajhg.2019.02.016;
RG Deciphering Developmental Disorders Study;
RG SYNAPS Study Group;
RA Salpietro V., Malintan N.T., Llano-Rivas I., Spaeth C.G., Efthymiou S.,
RA Striano P., Vandrovcova J., Cutrupi M.C., Chimenz R., David E., Di Rosa G.,
RA Marce-Grau A., Raspall-Chaure M., Martin-Hernandez E., Zara F., Minetti C.,
RA Bello O.D., De Zorzi R., Fortuna S., Dauber A., Alkhawaja M., Sultan T.,
RA Mankad K., Vitobello A., Thomas Q., Mau-Them F.T., Faivre L.,
RA Martinez-Azorin F., Prada C.E., Macaya A., Kullmann D.M., Rothman J.E.,
RA Krishnakumar S.S., Houlden H.;
RT "Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane
RT Fusion and Impair Human Neurodevelopment.";
RL Am. J. Hum. Genet. 104:721-730(2019).
CC -!- FUNCTION: Involved in the targeting and/or fusion of transport vesicles
CC to their target membrane (By similarity). Major SNARE protein of
CC synaptic vesicles which mediates fusion of synaptic vesicles to release
CC neurotransmitters. Essential for fast vesicular exocytosis and
CC activity-dependent neurotransmitter release as well as fast endocytosis
CC that mediates rapid reuse of synaptic vesicles (By similarity)
CC (PubMed:30929742). Modulates the gating characteristics of the delayed
CC rectifier voltage-dependent potassium channel KCNB1.
CC {ECO:0000250|UniProtKB:P63044, ECO:0000250|UniProtKB:P63045,
CC ECO:0000269|PubMed:30929742}.
CC -!- SUBUNIT: Part of the SNARE core complex containing SNAP25, VAMP2 and
CC STX1A. This complex binds to CPLX1. Interacts with BVES and STX4 (By
CC similarity). Interacts with VAPA and VAPB. Interacts with WDFY2, PRKCZ
CC and PRKCI (PubMed:17313651). Forms a complex with WDFY2 and PRKCZ
CC (PubMed:17313651). Interacts (via N-terminus) with KCNB1 (via N-
CC terminus and C-terminus); stimulates the channel inactivation rate of
CC KCNB1 (By similarity). Interacts with SEPT8; the interaction inhibits
CC interaction of VAMP2 with SYP. Interacts with SYP; the interaction is
CC inhibited by interaction with SEPT8 (By similarity). Interacts with
CC PICALM (PubMed:22118466, PubMed:21808019). Interacts with alpha-
CC synuclein/SNCA (PubMed:20798282). Interacts with STX3 (By similarity).
CC {ECO:0000250|UniProtKB:P63044, ECO:0000250|UniProtKB:P63045,
CC ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:20798282,
CC ECO:0000269|PubMed:21808019, ECO:0000269|PubMed:22118466}.
CC -!- INTERACTION:
CC P63027; Q13520: AQP6; NbExp=3; IntAct=EBI-520113, EBI-13059134;
CC P63027; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-520113, EBI-11343438;
CC P63027; Q9HA82: CERS4; NbExp=3; IntAct=EBI-520113, EBI-2622997;
CC P63027; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-520113, EBI-6942903;
CC P63027; Q15125: EBP; NbExp=3; IntAct=EBI-520113, EBI-3915253;
CC P63027; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-520113, EBI-781551;
CC P63027; P31937: HIBADH; NbExp=3; IntAct=EBI-520113, EBI-11427100;
CC P63027; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-520113, EBI-18053395;
CC P63027; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-520113, EBI-10266796;
CC P63027; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-520113, EBI-749265;
CC P63027; Q5T0T0: MARCHF8; NbExp=3; IntAct=EBI-520113, EBI-14061946;
CC P63027; O94806: PRKD3; NbExp=7; IntAct=EBI-520113, EBI-1255366;
CC P63027; Q9NY72: SCN3B; NbExp=3; IntAct=EBI-520113, EBI-17247926;
CC P63027; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-520113, EBI-10262251;
CC P63027; Q8TBB6: SLC7A14; NbExp=3; IntAct=EBI-520113, EBI-5235586;
CC P63027; O95721: SNAP29; NbExp=3; IntAct=EBI-520113, EBI-490676;
CC P63027; P37840: SNCA; NbExp=5; IntAct=EBI-520113, EBI-985879;
CC P63027; Q16623: STX1A; NbExp=5; IntAct=EBI-520113, EBI-712466;
CC P63027; P61266: STX1B; NbExp=3; IntAct=EBI-520113, EBI-9071709;
CC P63027; P32856-2: STX2; NbExp=3; IntAct=EBI-520113, EBI-11956649;
CC P63027; Q12846: STX4; NbExp=6; IntAct=EBI-520113, EBI-744942;
CC P63027; Q96IK0: TMEM101; NbExp=3; IntAct=EBI-520113, EBI-3922699;
CC P63027; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-520113, EBI-2548832;
CC P63027; P55072: VCP; NbExp=3; IntAct=EBI-520113, EBI-355164;
CC P63027; Q3ZAQ7: VMA21; NbExp=3; IntAct=EBI-520113, EBI-1055364;
CC P63027; A7GBG3: F; Xeno; NbExp=2; IntAct=EBI-520113, EBI-7604673;
CC P63027; Q57236: F; Xeno; NbExp=3; IntAct=EBI-520113, EBI-15790260;
CC P63027; O55012: Picalm; Xeno; NbExp=2; IntAct=EBI-520113, EBI-915601;
CC P63027; D2KHQ9; Xeno; NbExp=2; IntAct=EBI-520113, EBI-7604762;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000269|PubMed:17313651}; Single-pass type IV
CC membrane protein {ECO:0000255}. Cell membrane
CC {ECO:0000250|UniProtKB:P63045}. Note=Colocalizes with PRKCZ and WDFY2
CC in intracellular vesicles (PubMed:17313651).
CC {ECO:0000269|PubMed:17313651}.
CC -!- TISSUE SPECIFICITY: Nervous system and skeletal muscle.
CC {ECO:0000269|PubMed:8760387}.
CC -!- PTM: Phosphorylated by PRKCZ in vitro and this phosphorylation is
CC increased in the presence of WDFY2. {ECO:0000269|PubMed:17313651}.
CC -!- PTM: (Microbial infection) Targeted and hydrolyzed by C.botulinum
CC neurotoxin type B (BoNT/B, botB) which hydrolyzes the 76-Gln-|-Phe-77
CC bond and probably inhibits neurotransmitter release (PubMed:7803399).
CC {ECO:0000269|PubMed:7803399, ECO:0000305|PubMed:22289120}.
CC -!- PTM: (Microbial infection) Targeted and hydrolyzed by C.botulinum
CC neurotoxin type D (BoNT/D, botD) which probably hydrolyzes the 59-
CC Lys-|-Leu-60 bond and inhibits neurotransmitter release
CC (PubMed:22289120). Note that humans are not known to be infected by
CC C.botulinum type D. {ECO:0000269|PubMed:22289120, ECO:0000305,
CC ECO:0000305|PubMed:22289120}.
CC -!- PTM: (Microbial infection) Targeted and hydrolyzed by C.botulinum
CC neurotoxin type F (BoNT/F, botF) which hydrolyzes the 58-Gln-|-Lys-59
CC bond and probably inhibits neurotransmitter release (PubMed:19543288).
CC {ECO:0000305|PubMed:19543288, ECO:0000305|PubMed:22289120}.
CC -!- PTM: (Microbial infection) Targeted and hydrolyzed by C.tetani tetanus
CC toxin (tetX) which hydrolyzes the 76-Gln-|-Phe-77 bond and probably
CC inhibits neurotransmitter release (PubMed:7803399).
CC {ECO:0000269|PubMed:7803399}.
CC -!- DISEASE: Neurodevelopmental disorder with hypotonia and autistic
CC features with or without hyperkinetic movements (NEDHAHM) [MIM:618760]:
CC An autosomal dominant disorder characterized by axial hypotonia
CC apparent at birth, global developmental delay, intellectual disability,
CC seizures, and autistic features. Involuntary hyperkinetic movements are
CC present in some patients. {ECO:0000269|PubMed:30929742}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the synaptobrevin family. {ECO:0000305}.
CC -!- CAUTION: A structure of a fragment of this protein in complex with the
CC catalytic domain of C.botulinum neurotoxin type B (BoNT/B, botB) was
CC reported; because of the lack of clear and continuous electron density
CC for the VAMP2 peptide in the complex structure, the paper was retracted
CC (PubMed:10932255, PubMed:19578378). However this protein is a substrate
CC for BoNT/B (PubMed:7803399, PubMed:22289120).
CC {ECO:0000269|PubMed:10932255, ECO:0000269|PubMed:19578378,
CC ECO:0000269|PubMed:7803399, ECO:0000305|PubMed:22289120}.
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DR EMBL; M36205; AAA60604.1; -; Genomic_DNA.
DR EMBL; M36201; AAA60604.1; JOINED; Genomic_DNA.
DR EMBL; M36202; AAA60604.1; JOINED; Genomic_DNA.
DR EMBL; M36203; AAA60604.1; JOINED; Genomic_DNA.
DR EMBL; M36204; AAA60604.1; JOINED; Genomic_DNA.
DR EMBL; AJ225044; CAA12385.1; -; mRNA.
DR EMBL; AF135372; AAF15551.1; -; Genomic_DNA.
DR EMBL; AK289555; BAF82244.1; -; mRNA.
DR EMBL; CH471108; EAW90087.1; -; Genomic_DNA.
DR EMBL; BC002737; AAH02737.3; -; mRNA.
DR EMBL; BC019608; AAH19608.1; -; mRNA.
DR EMBL; BC033870; AAH33870.1; -; mRNA.
DR CCDS; CCDS32561.1; -.
DR PIR; B38315; B38315.
DR RefSeq; NP_055047.2; NM_014232.2.
DR PDB; 3FIE; X-ray; 2.10 A; C/D=25-57.
DR PDB; 3FII; X-ray; 2.17 A; B=32-57.
DR PDB; 3RK2; X-ray; 2.20 A; A/E=28-60.
DR PDB; 3RK3; X-ray; 3.50 A; A=28-60.
DR PDB; 3RL0; X-ray; 3.80 A; A/E/I/M/Q/U/Y/c=28-60.
DR PDB; 7UDC; EM; 3.70 A; C=29-83.
DR PDBsum; 3FIE; -.
DR PDBsum; 3FII; -.
DR PDBsum; 3RK2; -.
DR PDBsum; 3RK3; -.
DR PDBsum; 3RL0; -.
DR PDBsum; 7UDC; -.
DR AlphaFoldDB; P63027; -.
DR BMRB; P63027; -.
DR SMR; P63027; -.
DR BioGRID; 112711; 177.
DR CORUM; P63027; -.
DR DIP; DIP-39072N; -.
DR IntAct; P63027; 58.
DR MINT; P63027; -.
DR STRING; 9606.ENSP00000314214; -.
DR ChEMBL; CHEMBL2364160; -.
DR DrugBank; DB00042; Botulinum toxin type B.
DR TCDB; 1.F.1.1.1; the synaptosomal vesicle fusion pore (svf-pore) family.
DR iPTMnet; P63027; -.
DR MetOSite; P63027; -.
DR PhosphoSitePlus; P63027; -.
DR SwissPalm; P63027; -.
DR BioMuta; VAMP2; -.
DR DMDM; 288558837; -.
DR EPD; P63027; -.
DR jPOST; P63027; -.
DR MassIVE; P63027; -.
DR MaxQB; P63027; -.
DR PaxDb; P63027; -.
DR PeptideAtlas; P63027; -.
DR PRIDE; P63027; -.
DR ProteomicsDB; 57471; -.
DR TopDownProteomics; P63027; -.
DR Antibodypedia; 24568; 294 antibodies from 35 providers.
DR DNASU; 6844; -.
DR Ensembl; ENST00000316509.11; ENSP00000314214.6; ENSG00000220205.9.
DR GeneID; 6844; -.
DR KEGG; hsa:6844; -.
DR MANE-Select; ENST00000316509.11; ENSP00000314214.6; NM_014232.3; NP_055047.2.
DR UCSC; uc010cnt.2; human.
DR CTD; 6844; -.
DR DisGeNET; 6844; -.
DR GeneCards; VAMP2; -.
DR HGNC; HGNC:12643; VAMP2.
DR HPA; ENSG00000220205; Low tissue specificity.
DR MalaCards; VAMP2; -.
DR MIM; 185881; gene.
DR MIM; 618760; phenotype.
DR neXtProt; NX_P63027; -.
DR OpenTargets; ENSG00000220205; -.
DR PharmGKB; PA37267; -.
DR VEuPathDB; HostDB:ENSG00000220205; -.
DR eggNOG; KOG0860; Eukaryota.
DR GeneTree; ENSGT00940000158370; -.
DR InParanoid; P63027; -.
DR OMA; CQDTFAT; -.
DR PhylomeDB; P63027; -.
DR TreeFam; TF313666; -.
DR PathwayCommons; P63027; -.
DR Reactome; R-HSA-1445148; Translocation of SLC2A4 (GLUT4) to the plasma membrane.
DR Reactome; R-HSA-181429; Serotonin Neurotransmitter Release Cycle.
DR Reactome; R-HSA-181430; Norepinephrine Neurotransmitter Release Cycle.
DR Reactome; R-HSA-199992; trans-Golgi Network Vesicle Budding.
DR Reactome; R-HSA-210500; Glutamate Neurotransmitter Release Cycle.
DR Reactome; R-HSA-212676; Dopamine Neurotransmitter Release Cycle.
DR Reactome; R-HSA-264642; Acetylcholine Neurotransmitter Release Cycle.
DR Reactome; R-HSA-264876; Insulin processing.
DR Reactome; R-HSA-422356; Regulation of insulin secretion.
DR Reactome; R-HSA-432720; Lysosome Vesicle Biogenesis.
DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-HSA-449836; Other interleukin signaling.
DR Reactome; R-HSA-5250955; Toxicity of botulinum toxin type D (botD).
DR Reactome; R-HSA-5250958; Toxicity of botulinum toxin type B (botB).
DR Reactome; R-HSA-5250981; Toxicity of botulinum toxin type F (botF).
DR Reactome; R-HSA-5250982; Toxicity of tetanus toxin (tetX).
DR Reactome; R-HSA-5250989; Toxicity of botulinum toxin type G (botG).
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-888590; GABA synthesis, release, reuptake and degradation.
DR Reactome; R-HSA-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR SignaLink; P63027; -.
DR SIGNOR; P63027; -.
DR BioGRID-ORCS; 6844; 9 hits in 1064 CRISPR screens.
DR ChiTaRS; VAMP2; human.
DR EvolutionaryTrace; P63027; -.
DR GeneWiki; VAMP2; -.
DR GenomeRNAi; 6844; -.
DR Pharos; P63027; Tbio.
DR PRO; PR:P63027; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P63027; protein.
DR Bgee; ENSG00000220205; Expressed in Brodmann (1909) area 10 and 198 other tissues.
DR ExpressionAtlas; P63027; baseline and differential.
DR Genevisible; P63027; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
DR GO; GO:0061202; C:clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane; TAS:Reactome.
DR GO; GO:0060203; C:clathrin-sculpted glutamate transport vesicle membrane; TAS:Reactome.
DR GO; GO:0070083; C:clathrin-sculpted monoamine transport vesicle membrane; TAS:Reactome.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISS:ParkinsonsUK-UCL.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:ParkinsonsUK-UCL.
DR GO; GO:0044306; C:neuron projection terminus; ISS:ParkinsonsUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005886; C:plasma membrane; ISS:ParkinsonsUK-UCL.
DR GO; GO:0030141; C:secretory granule; ISS:ParkinsonsUK-UCL.
DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome.
DR GO; GO:0031201; C:SNARE complex; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; ISS:ParkinsonsUK-UCL.
DR GO; GO:0008021; C:synaptic vesicle; ISS:ParkinsonsUK-UCL.
DR GO; GO:0030672; C:synaptic vesicle membrane; ISS:ParkinsonsUK-UCL.
DR GO; GO:0070044; C:synaptobrevin 2-SNAP-25-syntaxin-1a complex; ISS:ParkinsonsUK-UCL.
DR GO; GO:0070032; C:synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex; ISS:ParkinsonsUK-UCL.
DR GO; GO:0070033; C:synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005802; C:trans-Golgi network; ISS:ParkinsonsUK-UCL.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0042589; C:zymogen granule membrane; ISS:ParkinsonsUK-UCL.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005516; F:calmodulin binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005543; F:phospholipid binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0043621; F:protein self-association; TAS:ParkinsonsUK-UCL.
DR GO; GO:0005484; F:SNAP receptor activity; IBA:GO_Central.
DR GO; GO:0000149; F:SNARE binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0019905; F:syntaxin binding; IPI:UniProtKB.
DR GO; GO:0017075; F:syntaxin-1 binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; ISS:ParkinsonsUK-UCL.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:ParkinsonsUK-UCL.
DR GO; GO:0043308; P:eosinophil degranulation; IMP:UniProtKB.
DR GO; GO:0006887; P:exocytosis; TAS:ParkinsonsUK-UCL.
DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; ISS:ParkinsonsUK-UCL.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISS:ParkinsonsUK-UCL.
DR GO; GO:0061025; P:membrane fusion; ISS:ParkinsonsUK-UCL.
DR GO; GO:0090316; P:positive regulation of intracellular protein transport; ISS:ParkinsonsUK-UCL.
DR GO; GO:0015031; P:protein transport; ISS:ParkinsonsUK-UCL.
DR GO; GO:0065003; P:protein-containing complex assembly; ISS:ParkinsonsUK-UCL.
DR GO; GO:1902259; P:regulation of delayed rectifier potassium channel activity; ISS:UniProtKB.
DR GO; GO:0017157; P:regulation of exocytosis; ISS:ParkinsonsUK-UCL.
DR GO; GO:0060627; P:regulation of vesicle-mediated transport; ISS:ParkinsonsUK-UCL.
DR GO; GO:0009749; P:response to glucose; ISS:ParkinsonsUK-UCL.
DR GO; GO:0035493; P:SNARE complex assembly; IBA:GO_Central.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; ISS:UniProtKB.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; ISS:ParkinsonsUK-UCL.
DR GO; GO:0006906; P:vesicle fusion; IMP:UniProtKB.
DR GO; GO:0016192; P:vesicle-mediated transport; ISS:ParkinsonsUK-UCL.
DR InterPro; IPR001388; Synaptobrevin.
DR InterPro; IPR016444; Synaptobrevin/VAMP.
DR InterPro; IPR042855; V_SNARE_CC.
DR InterPro; IPR028717; VAMP2.
DR PANTHER; PTHR45701; PTHR45701; 1.
DR PANTHER; PTHR45701:SF5; PTHR45701:SF5; 1.
DR Pfam; PF00957; Synaptobrevin; 1.
DR PIRSF; PIRSF005409; Synaptobrevin_euk; 1.
DR PRINTS; PR00219; SYNAPTOBREVN.
DR PROSITE; PS00417; SYNAPTOBREVIN; 1.
DR PROSITE; PS50892; V_SNARE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell membrane; Coiled coil; Cytoplasmic vesicle;
KW Disease variant; Intellectual disability; Membrane; Phosphoprotein;
KW Reference proteome; Synapse; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P63026"
FT CHAIN 2..116
FT /note="Vesicle-associated membrane protein 2"
FT /id="PRO_0000206723"
FT TOPO_DOM 2..94
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..114
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 115..116
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT DOMAIN 31..91
FT /note="v-SNARE coiled-coil homology"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00290"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 92..116
FT /note="Required for interaction with SEPT8"
FT /evidence="ECO:0000250|UniProtKB:P63045"
FT SITE 58..59
FT /note="(Microbial infection) Cleavage; by C.botulinum
FT neurotoxin type F (BoNT/F, botF)"
FT /evidence="ECO:0000305|PubMed:19543288"
FT SITE 76..77
FT /note="(Microbial infection) Cleavage; by C.botulinum
FT neurotoxin type D (BoNT/D, botD)"
FT /evidence="ECO:0000269|PubMed:7803399"
FT SITE 76..77
FT /note="(Microbial infection) Cleavage; by C.tetani toxin
FT (tetX)"
FT /evidence="ECO:0000269|PubMed:7803399"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P63026"
FT VARIANT 43
FT /note="Missing (in NEDHAHM)"
FT /evidence="ECO:0000269|PubMed:30929742"
FT /id="VAR_083584"
FT VARIANT 45
FT /note="Missing (in NEDHAHM)"
FT /evidence="ECO:0000269|PubMed:30929742"
FT /id="VAR_083585"
FT VARIANT 75
FT /note="S -> P (in NEDHAHM; impaired vesicle fusion;
FT dbSNP:rs1598265387)"
FT /evidence="ECO:0000269|PubMed:30929742"
FT /id="VAR_083586"
FT VARIANT 77
FT /note="F -> S (in NEDHAHM; dbSNP:rs1598265384)"
FT /evidence="ECO:0000269|PubMed:30929742"
FT /id="VAR_083587"
FT VARIANT 78
FT /note="E -> A (in NEDHAHM; no effect on vesicle fusion;
FT dbSNP:rs1598265382)"
FT /evidence="ECO:0000269|PubMed:30929742"
FT /id="VAR_083588"
FT MUTAGEN 28
FT /note="S->A: Significant loss of phosphorylation; when
FT associated with A-61, A-75 and A-80."
FT /evidence="ECO:0000269|PubMed:17313651"
FT MUTAGEN 41
FT /note="E->A: 70% reduction in cleavage by C.botulinum
FT neurotoxin type F (BoNT/F, botF)."
FT /evidence="ECO:0000269|PubMed:19543288"
FT MUTAGEN 50
FT /note="V->D: 65% reduction in cleavage by BoNT/F."
FT /evidence="ECO:0000269|PubMed:19543288"
FT MUTAGEN 53..54
FT /note="VL->DD: 98% reduction in cleavage by BoNT/F."
FT /evidence="ECO:0000269|PubMed:19543288"
FT MUTAGEN 53
FT /note="V->A: Wild-type cleavage by BoNT/F."
FT /evidence="ECO:0000269|PubMed:19543288"
FT MUTAGEN 53
FT /note="V->D: 90% reduction in cleavage by BoNT/F."
FT /evidence="ECO:0000269|PubMed:19543288"
FT MUTAGEN 61
FT /note="S->A: Significant loss of phosphorylation; when
FT associated with A-28, A-75 and A-80."
FT /evidence="ECO:0000269|PubMed:17313651"
FT MUTAGEN 75
FT /note="S->A: Significant loss of phosphorylation; when
FT associated with A-28, A-61 and A-80."
FT /evidence="ECO:0000269|PubMed:17313651"
FT MUTAGEN 80
FT /note="S->A: Significant loss of phosphorylation; when
FT associated with A-28, A-61 and A-75."
FT /evidence="ECO:0000269|PubMed:17313651"
FT CONFLICT 116
FT /note="T -> S (in Ref. 1; AAA60604, 2; CAA12385 and 3;
FT AAF15551)"
FT /evidence="ECO:0000305"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:3FIE"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:3FIE"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:3FIE"
SQ SEQUENCE 116 AA; 12663 MW; 9CD679C4F6F1B5A8 CRC64;
MSATAATAPP AAPAGEGGPP APPPNLTSNR RLQQTQAQVD EVVDIMRVNV DKVLERDQKL
SELDDRADAL QAGASQFETS AAKLKRKYWW KNLKMMIILG VICAIILIII IVYFST
