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Protein

Synaptosomal-associated protein 25

Gene

SNAP25

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

t-SNARE involved in the molecular regulation of neurotransmitter release. May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion. Regulates plasma membrane recycling through its interaction with CENPF. Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 in pancreatic beta cells.By similarity

Miscellaneous

When cloned and expressed in E.coli, where protein palmitoylation does not occur, Cys-85, Cys-88, Cys-90 and Cys-92 in the protein sequence readily form an iron-sulfur cluster.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei180 – 181(Microbial infection) Cleavage; by C.botulinum neurotoxin type E (BoNT/E)1 Publication2
Sitei197 – 198(Microbial infection) Cleavage; by C.botulinum neurotoxin type A (BoNT/A, botA)1 Publication1 Publication2
Sitei198 – 199(Microbial infection) Cleavage; by C.botulinum neurotoxin type C (BoNT/C)1 Publication1 Publication2

GO - Molecular functioni

  • calcium-dependent protein binding Source: ParkinsonsUK-UCL
  • SNAP receptor activity Source: GO_Central
  • syntaxin-1 binding Source: UniProtKB

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-181429 Serotonin Neurotransmitter Release Cycle
R-HSA-181430 Norepinephrine Neurotransmitter Release Cycle
R-HSA-210500 Glutamate Neurotransmitter Release Cycle
R-HSA-212676 Dopamine Neurotransmitter Release Cycle
R-HSA-264642 Acetylcholine Neurotransmitter Release Cycle
R-HSA-422356 Regulation of insulin secretion
R-HSA-449836 Other interleukin signaling
R-HSA-5250968 Toxicity of botulinum toxin type A (BoNT/A)
R-HSA-5250971 Toxicity of botulinum toxin type C (BoNT/C)
R-HSA-5250992 Toxicity of botulinum toxin type E (BoNT/E)
R-HSA-6798695 Neutrophil degranulation
R-HSA-888590 GABA synthesis, release, reuptake and degradation
SIGNORiP60880

Protein family/group databases

TCDBi1.F.1.1.1 the synaptosomal vesicle fusion pore (svf-pore) family

Names & Taxonomyi

Protein namesi
Recommended name:
Synaptosomal-associated protein 25
Short name:
SNAP-25
Alternative name(s):
Super protein
Short name:
SUP
Synaptosomal-associated 25 kDa protein
Gene namesi
Name:SNAP25
Synonyms:SNAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000132639.12
HGNCiHGNC:11132 SNAP25
MIMi600322 gene
neXtProtiNX_P60880

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Membrane, Synapse, Synaptosome

Pathology & Biotechi

Involvement in diseasei

Myasthenic syndrome, congenital, 18 (CMS18)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS18 is an autosomal dominant presynaptic disorder clinically characterized by early-onset muscle weakness and easy fatigability associated with delayed psychomotor development and ataxia.
See also OMIM:616330
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07369867I → N in CMS18; interfers with calcium-induced fusion; inhibits exocytosis of catecholamine-containing vesicles. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi112V → A: Mildly decreased binding affinity for ZDHHC17. 1 Publication1
Mutagenesisi113V → A: Mildly decreased binding affinity for ZDHHC17. 1 Publication1
Mutagenesisi115S → A: No effect on ZDHHC17 binding. 1 Publication1
Mutagenesisi116Q → A: Decreased binding affinity for ZDHHC17. 1 Publication1
Mutagenesisi117P → A: Decreased binding affinity for ZDHHC17. 1 Publication1
Mutagenesisi119R → A: No effect on ZDHHC17 binding. 1 Publication1
Mutagenesisi152Q → A: Decreased cleavage by C.botulinum BoNT/C, no change in cleavage by C.botulinum BoNT/A (botA). 1 Publication1
Mutagenesisi156I → E: Small decrease in affinity for C.botulinum BoNT/A, increased efficiency of BoNT/C cleavage. 2 Publications1
Mutagenesisi166D → A: Decreased cleavage by BoNT/C, no change in cleavage by BoNT/A. 1 Publication1
Mutagenesisi167M → E: Small decrease in affinity for C.botulinum BoNT/A. 1 Publication1
Mutagenesisi199A → R: Not cleaved by BoNT/C. 1 Publication1
Mutagenesisi202M → Y: Slight decrease in affinity for BoNT/A, increases kcat for BoNT/A. 1 Publication1

Keywords - Diseasei

Congenital myasthenic syndrome, Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi6616
MalaCardsiSNAP25
MIMi616330 phenotype
OpenTargetsiENSG00000132639
PharmGKBiPA35980

Chemistry databases

ChEMBLiCHEMBL2364159
DrugBankiDB00083 Botulinum Toxin Type A

Polymorphism and mutation databases

BioMutaiSNAP25
DMDMi46397726

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002135871 – 206Synaptosomal-associated protein 25Add BLAST206

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi85S-palmitoyl cysteineBy similarity1
Lipidationi88S-palmitoyl cysteineBy similarity1
Lipidationi90S-palmitoyl cysteineBy similarity1
Lipidationi92S-palmitoyl cysteineBy similarity1
Modified residuei138PhosphothreonineBy similarity1
Modified residuei154PhosphoserineBy similarity1
Modified residuei187PhosphoserineBy similarity1

Post-translational modificationi

Palmitoylated (PubMed:28757145). Cys-85 appears to be the main site, and palmitoylation is required for membrane association (By similarity).By similarity1 Publication
(Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type A (BoNT/A, botA) which hydrolyzes the 197-Gln-|-Arg-198 bond and inhibits neurotransmitter release (PubMed:15592454, PubMed:9886085).1 Publication1 Publication
(Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type C (BoNT/C) which hydrolyzes the 198-Arg-|-Ala-199 bond and inhibits neurotransmitter release (PubMed:9886085, PubMed:17718519). C.botulinum type C only rarely infects humans.2 Publications
(Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type E (BoNT/E) which hydrolyzes the 180-Arg-|-Ile-181 bond and inhibits neurotransmitter release (PubMed:9886085).1 Publication

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiP60880
MaxQBiP60880
PaxDbiP60880
PeptideAtlasiP60880
PRIDEiP60880
ProteomicsDBi57231
57232 [P60880-2]

PTM databases

iPTMnetiP60880
PhosphoSitePlusiP60880
SwissPalmiP60880

Miscellaneous databases

PMAP-CutDBiQ5U0B5

Expressioni

Tissue specificityi

Neurons of the neocortex, hippocampus, piriform cortex, anterior thalamic nuclei, pontine nuclei, and granule cells of the cerebellum.

Gene expression databases

BgeeiENSG00000132639
CleanExiHS_SNAP25
ExpressionAtlasiP60880 baseline and differential
GenevisibleiP60880 HS

Organism-specific databases

HPAiCAB000360
HPA001830

Interactioni

Subunit structurei

Part of the SNARE core complex containing SNAP25, VAMP2 and STX1A; this complex binds CPLX1 (PubMed:11832227). Found in a complex containing SYT1, SV2B and syntaxin-1 (By similarity). Found in a ternary complex with STX1A and VAMP8 (By similarity). Isoform 1 and isoform 2 interact with BLOC1S6 (PubMed:19546860). Interacts with CENPF (By similarity). Interacts with EQTN (By similarity). Interacts with HGS (By similarity). Interacts with KCNB1 (via N-terminus); reduces the voltage-dependent potassium channel KCNB1 activity in pancreatic beta cells (By similarity). Interacts with OTOF (By similarity). Interacts with RIMS1 (By similarity). Interacts with SNAPIN (By similarity). Interacts with STXBP6 (By similarity). Interacts with TRIM9 (By similarity). Interacts with ZDHHC13 (via ANK repeats) (By similarity). Interacts with ZDHHC17 (via ANK repeats) (PubMed:28882895, PubMed:28757145). Interacts with PLCL1 (via C2 domain) (By similarity). Associates with the BLOC-1 complex (PubMed:19546860). Interacts with PRRT2; this interaction may impair the formation of the SNARE complex (PubMed:22832103, PubMed:25915028).By similarity6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • calcium-dependent protein binding Source: ParkinsonsUK-UCL
  • SNAP receptor activity Source: GO_Central
  • syntaxin-1 binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112500, 33 interactors
CORUMiP60880
DIPiDIP-34554N
IntActiP60880, 19 interactors
MINTiP60880
STRINGi9606.ENSP00000254976

Structurei

Secondary structure

1206
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi8 – 80Combined sources73
Helixi148 – 167Combined sources20
Beta strandi191 – 193Combined sources3

3D structure databases

ProteinModelPortaliP60880
SMRiP60880
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP60880

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini19 – 81t-SNARE coiled-coil homology 1PROSITE-ProRule annotationAdd BLAST63
Domaini140 – 202t-SNARE coiled-coil homology 2PROSITE-ProRule annotationAdd BLAST63

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 75Interaction with CENPFBy similarityAdd BLAST75
Regioni111 – 120Interaction with ZDHHC171 Publication10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi85 – 92Cys-rich8

Sequence similaritiesi

Belongs to the SNAP-25 family.Curated

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG3065 Eukaryota
ENOG410Y3Y0 LUCA
GeneTreeiENSGT00390000012186
HOVERGENiHBG056971
InParanoidiP60880
KOiK18211
OMAiGEMDENL
OrthoDBiEOG091G0N7J
PhylomeDBiP60880
TreeFamiTF315125

Family and domain databases

InterProiView protein in InterPro
IPR000928 SNAP-25
IPR039077 SNAP25
IPR000727 T_SNARE_dom
PANTHERiPTHR19305:SF5 PTHR19305:SF5, 1 hit
PfamiView protein in Pfam
PF00835 SNAP-25, 1 hit
SMARTiView protein in SMART
SM00397 t_SNARE, 2 hits
PROSITEiView protein in PROSITE
PS50192 T_SNARE, 2 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Isoforms differ by the usage of two alternative homologous exons (5a and 5b) which code for positions 56 to 94 and differ only in 9 positions out of 39.
Isoform 1 (identifier: P60880-1) [UniParc]FASTAAdd to basket
Also known as: SNAP-25b

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAEDADMRNE LEEMQRRADQ LADESLESTR RMLQLVEESK DAGIRTLVML
60 70 80 90 100
DEQGEQLERI EEGMDQINKD MKEAEKNLTD LGKFCGLCVC PCNKLKSSDA
110 120 130 140 150
YKKAWGNNQD GVVASQPARV VDEREQMAIS GGFIRRVTND ARENEMDENL
160 170 180 190 200
EQVSGIIGNL RHMALDMGNE IDTQNRQIDR IMEKADSNKT RIDEANQRAT

KMLGSG
Length:206
Mass (Da):23,315
Last modified:April 13, 2004 - v1
Checksum:iFBED2B082A4CB6A6
GO
Isoform 2 (identifier: P60880-2) [UniParc] [UniParc]FASTAAdd to basket
Also known as: SNAP-25a

The sequence of this isoform differs from the canonical sequence as follows:
     58-89: ERIEEGMDQINKDMKEAEKNLTDLGKFCGLCV → DRVEEGMNHINQDMKEAEKNLKDLGKCCGLFI

Show »
Length:206
Mass (Da):23,336
Checksum:iE272652C701EA984
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti44I → V in BAD97337 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07369867I → N in CMS18; interfers with calcium-induced fusion; inhibits exocytosis of catecholamine-containing vesicles. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00618658 – 89ERIEE…CGLCV → DRVEEGMNHINQDMKEAEKN LKDLGKCCGLFI in isoform 2. 5 PublicationsAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L19760 mRNA Translation: AAC37545.1
L19761 mRNA Translation: AAC37546.1
D21267 mRNA Translation: BAA22370.1
BT019684 mRNA Translation: AAV38490.1
AK223617 mRNA Translation: BAD97337.1
AK289647 mRNA Translation: BAF82336.1
AK314359 mRNA Translation: BAG36991.1
AL023913 Genomic DNA No translation available.
CH471133 Genomic DNA Translation: EAX10346.1
CH471133 Genomic DNA Translation: EAX10349.1
CH471133 Genomic DNA Translation: EAX10350.1
CH471133 Genomic DNA Translation: EAX10352.1
BC010647 mRNA Translation: AAH10647.1
CCDSiCCDS13109.1 [P60880-2]
CCDS13110.1
PIRiI53735
I67823
RefSeqiNP_001309831.1, NM_001322902.1 [P60880-2]
NP_001309832.1, NM_001322903.1 [P60880-1]
NP_001309833.1, NM_001322904.1 [P60880-1]
NP_001309834.1, NM_001322905.1 [P60880-1]
NP_001309835.1, NM_001322906.1 [P60880-1]
NP_001309836.1, NM_001322907.1 [P60880-1]
NP_001309837.1, NM_001322908.1 [P60880-1]
NP_001309838.1, NM_001322909.1 [P60880-1]
NP_001309839.1, NM_001322910.1 [P60880-1]
NP_003072.2, NM_003081.4 [P60880-2]
NP_570824.1, NM_130811.3 [P60880-1]
XP_005260865.1, XM_005260808.4 [P60880-1]
XP_016883510.1, XM_017028021.1 [P60880-2]
XP_016883511.1, XM_017028022.1 [P60880-2]
UniGeneiHs.167317

Genome annotation databases

EnsembliENST00000254976; ENSP00000254976; ENSG00000132639 [P60880-1]
ENST00000304886; ENSP00000307341; ENSG00000132639 [P60880-2]
GeneIDi6616
KEGGihsa:6616
UCSCiuc002wnq.3 human

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSNP25_HUMAN
AccessioniPrimary (citable) accession number: P60880
Secondary accession number(s): B2RAU4
, D3DW16, D3DW17, P13795, P36974, P70557, P70558, Q53EM2, Q5U0B5, Q8IXK3, Q96FM2, Q9BR45
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 13, 2004
Last sequence update: April 13, 2004
Last modified: July 18, 2018
This is version 158 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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