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Protein

Synaptotagmin-1

Gene

SYT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. A Ca2+-dependent interaction between synaptotagmin and putative receptors for activated protein kinase C has also been reported. It can bind to at least three additional proteins in a Ca2+-independent manner; these are neurexins, syntaxin and AP2. Plays a role in dendrite formation by melanocytes (PubMed:23999003).1 Publication

Cofactori

Ca2+By similarityNote: Binds 3 Ca2+ ions per subunit. The ions are bound to the C2 domains.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi172Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi173Calcium 1By similarity1
Metal bindingi173Calcium 2By similarity1
Metal bindingi179Calcium 1By similarity1
Metal bindingi231Calcium 1By similarity1
Metal bindingi231Calcium 2By similarity1
Metal bindingi232Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi233Calcium 1By similarity1
Metal bindingi233Calcium 2By similarity1
Metal bindingi233Calcium 3By similarity1
Metal bindingi236Calcium 3By similarity1
Metal bindingi237Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi239Calcium 2By similarity1
Metal bindingi239Calcium 3By similarity1

GO - Molecular functioni

  • 1-phosphatidylinositol binding Source: UniProtKB
  • calcium-dependent phospholipid binding Source: ParkinsonsUK-UCL
  • calcium ion binding Source: GO_Central
  • clathrin binding Source: GO_Central
  • low-density lipoprotein particle receptor binding Source: MGI
  • phosphatidylinositol-4,5-bisphosphate binding Source: GO_Central
  • phosphatidylserine binding Source: Ensembl
  • SNARE binding Source: ParkinsonsUK-UCL
  • syntaxin-1 binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Differentiation

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000067715-MONOMER.
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-5250958. Toxicity of botulinum toxin type B (BoNT/B).
R-HSA-5250989. Toxicity of botulinum toxin type G (BoNT/G).
R-HSA-6794361. Interactions of neurexins and neuroligins at synapses.
R-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-HSA-8856828. Clathrin-mediated endocytosis.
R-HSA-888590. GABA synthesis, release, reuptake and degradation.

Protein family/group databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Synaptotagmin-1
Alternative name(s):
Synaptotagmin I
Short name:
SytI
p65
Gene namesi
Name:SYT1
Synonyms:SVP65, SYT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:11509. SYT1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 57VesicularSequence analysisAdd BLAST57
Transmembranei58 – 80HelicalSequence analysisAdd BLAST23
Topological domaini81 – 422CytoplasmicSequence analysisAdd BLAST342

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Cytoplasmic vesicle, Membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

A SYT1 rare mutation has been found in a child with a severe neuro-developmental disorder. The individual harboring this variant shows early onset dyskinetic movement disorder, severe motor delay and profound cognitive impairment, suggesting that SYT1 may play a role in the pathogenesis of this neuro-developmental disorder.

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6857.
OpenTargetsiENSG00000067715.
PharmGKBiPA36290.

Polymorphism and mutation databases

BioMutaiSYT1.
DMDMi135086.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001839361 – 422Synaptotagmin-1Add BLAST422

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi25N-linked (GlcNAc...)Sequence analysis1
Lipidationi75S-palmitoyl cysteineBy similarity1
Lipidationi76S-palmitoyl cysteineBy similarity1
Lipidationi78S-palmitoyl cysteineBy similarity1
Lipidationi80S-palmitoyl cysteineBy similarity1
Lipidationi83S-palmitoyl cysteineBy similarity1
Modified residuei126PhosphothreonineBy similarity1
Modified residuei129PhosphothreonineCombined sources1
Modified residuei230PhosphotyrosineBy similarity1
Modified residuei265PhosphoserineBy similarity1
Modified residuei343PhosphoserineBy similarity1
Modified residuei345PhosphoserineBy similarity1

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiP21579.
PaxDbiP21579.
PeptideAtlasiP21579.
PRIDEiP21579.

PTM databases

iPTMnetiP21579.
PhosphoSitePlusiP21579.
SwissPalmiP21579.

Miscellaneous databases

PMAP-CutDBP21579.

Expressioni

Tissue specificityi

Expressed in melanocytes (PubMed:23999003).1 Publication

Gene expression databases

BgeeiENSG00000067715.
CleanExiHS_SYT1.
ExpressionAtlasiP21579. baseline and differential.
GenevisibleiP21579. HS.

Organism-specific databases

HPAiHPA008394.
HPA064788.

Interactioni

Subunit structurei

Homotetramer (Probable). Interacts with SCAMP5, STON2, SV2A, SV2B, SV2C and RIMS1. Forms a complex with SV2B, syntaxin 1 and SNAP25 (By similarity).By similarityCurated

Binary interactionsi

WithEntry#Exp.IntActNotes
CACNB4O00305-22EBI-524909,EBI-714855
IKBKGQ9Y6K93EBI-524909,EBI-81279

GO - Molecular functioni

  • clathrin binding Source: GO_Central
  • low-density lipoprotein particle receptor binding Source: MGI
  • SNARE binding Source: ParkinsonsUK-UCL
  • syntaxin-1 binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112723. 40 interactors.
DIPiDIP-34042N.
IntActiP21579. 18 interactors.
MINTiMINT-1400342.
STRINGi9606.ENSP00000261205.

Structurei

Secondary structure

1422
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi37 – 47Combined sources11
Beta strandi145 – 153Combined sources9
Turni154 – 157Combined sources4
Beta strandi158 – 167Combined sources10
Helixi173 – 175Combined sources3
Beta strandi180 – 188Combined sources9
Beta strandi206 – 213Combined sources8
Helixi217 – 220Combined sources4
Beta strandi224 – 231Combined sources8
Beta strandi234 – 236Combined sources3
Beta strandi239 – 247Combined sources9
Helixi248 – 250Combined sources3
Beta strandi257 – 262Combined sources6
Beta strandi276 – 284Combined sources9
Turni285 – 288Combined sources4
Beta strandi289 – 299Combined sources11
Beta strandi304 – 307Combined sources4
Beta strandi311 – 319Combined sources9
Beta strandi322 – 328Combined sources7
Beta strandi333 – 337Combined sources5
Beta strandi339 – 347Combined sources9
Helixi350 – 352Combined sources3
Turni353 – 355Combined sources3
Beta strandi357 – 364Combined sources8
Beta strandi367 – 369Combined sources3
Beta strandi373 – 380Combined sources8
Helixi385 – 396Combined sources12
Beta strandi402 – 407Combined sources6
Helixi411 – 417Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2K45NMR-A141-268[»]
2K4ANMR-A141-268[»]
2K8MNMR-A/D141-268[»]
2KI6NMR-A/F141-268[»]
2LHANMR-A271-422[»]
2N1TNMR-E272-419[»]
2R83X-ray2.70A/B141-422[»]
3F00X-ray1.36A141-266[»]
3F01X-ray1.70A141-266[»]
3F04X-ray1.35A141-266[»]
3F05X-ray1.40A141-266[»]
4ISQX-ray2.65D/E/F33-53[»]
4V11X-ray1.95A273-422[»]
ProteinModelPortaliP21579.
SMRiP21579.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21579.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini157 – 245C2 1PROSITE-ProRule annotationAdd BLAST89
Domaini287 – 378C2 2PROSITE-ProRule annotationAdd BLAST92

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni136 – 382Phospholipid bindingCuratedAdd BLAST247

Domaini

The first C2 domain mediates Ca2+-dependent phospholipid binding.By similarity
The second C2 domain mediates interaction with SV2A and probably with STN2.By similarity

Sequence similaritiesi

Belongs to the synaptotagmin family.Curated
Contains 2 C2 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IT3Q. Eukaryota.
ENOG410Z15P. LUCA.
GeneTreeiENSGT00760000118973.
HOGENOMiHOG000232127.
HOVERGENiHBG005010.
InParanoidiP21579.
KOiK15290.
OMAiGEFKVAM.
OrthoDBiEOG091G0XMQ.
PhylomeDBiP21579.
TreeFamiTF315600.

Family and domain databases

Gene3Di2.60.40.150. 2 hits.
InterProiIPR000008. C2_dom.
IPR001565. Synaptotagmin.
IPR015428. Synaptotagmin1.
[Graphical view]
PANTHERiPTHR10024:SF239. PTHR10024:SF239. 1 hit.
PfamiPF00168. C2. 2 hits.
[Graphical view]
PRINTSiPR00360. C2DOMAIN.
PR00399. SYNAPTOTAGMN.
SMARTiSM00239. C2. 2 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 2 hits.
PROSITEiPS50004. C2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P21579-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVSESHHEAL AAPPVTTVAT VLPSNATEPA SPGEGKEDAF SKLKEKFMNE
60 70 80 90 100
LHKIPLPPWA LIAIAIVAVL LVLTCCFCIC KKCLFKKKNK KKGKEKGGKN
110 120 130 140 150
AINMKDVKDL GKTMKDQALK DDDAETGLTD GEEKEEPKEE EKLGKLQYSL
160 170 180 190 200
DYDFQNNQLL VGIIQAAELP ALDMGGTSDP YVKVFLLPDK KKKFETKVHR
210 220 230 240 250
KTLNPVFNEQ FTFKVPYSEL GGKTLVMAVY DFDRFSKHDI IGEFKVPMNT
260 270 280 290 300
VDFGHVTEEW RDLQSAEKEE QEKLGDICFS LRYVPTAGKL TVVILEAKNL
310 320 330 340 350
KKMDVGGLSD PYVKIHLMQN GKRLKKKKTT IKKNTLNPYY NESFSFEVPF
360 370 380 390 400
EQIQKVQVVV TVLDYDKIGK NDAIGKVFVG YNSTGAELRH WSDMLANPRR
410 420
PIAQWHTLQV EEEVDAMLAV KK
Length:422
Mass (Da):47,573
Last modified:May 1, 1991 - v1
Checksum:i467F7C58E411AFA9
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_072911368I → T Probable disease-associated mutation found in a patient with an early onset dyskinetic movement disorder, severe motor delay and profound cognitive impairment. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55047 mRNA. Translation: AAA60609.1.
AK094616 mRNA. Translation: BAG52897.1.
AK126908 mRNA. Translation: BAG54392.1.
CR627387 mRNA. Translation: CAH10483.1.
CH471054 Genomic DNA. Translation: EAW97343.1.
BC058917 mRNA. Translation: AAH58917.1.
CCDSiCCDS9017.1.
PIRiA39052. BMHU1Y.
RefSeqiNP_001129277.1. NM_001135805.1.
NP_001129278.1. NM_001135806.1.
NP_005630.1. NM_005639.2.
XP_011537012.1. XM_011538710.1.
XP_016875398.1. XM_017019909.1.
UniGeneiHs.310545.

Genome annotation databases

EnsembliENST00000261205; ENSP00000261205; ENSG00000067715.
ENST00000393240; ENSP00000376932; ENSG00000067715.
ENST00000552744; ENSP00000447575; ENSG00000067715.
GeneIDi6857.
KEGGihsa:6857.
UCSCiuc001sys.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55047 mRNA. Translation: AAA60609.1.
AK094616 mRNA. Translation: BAG52897.1.
AK126908 mRNA. Translation: BAG54392.1.
CR627387 mRNA. Translation: CAH10483.1.
CH471054 Genomic DNA. Translation: EAW97343.1.
BC058917 mRNA. Translation: AAH58917.1.
CCDSiCCDS9017.1.
PIRiA39052. BMHU1Y.
RefSeqiNP_001129277.1. NM_001135805.1.
NP_001129278.1. NM_001135806.1.
NP_005630.1. NM_005639.2.
XP_011537012.1. XM_011538710.1.
XP_016875398.1. XM_017019909.1.
UniGeneiHs.310545.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2K45NMR-A141-268[»]
2K4ANMR-A141-268[»]
2K8MNMR-A/D141-268[»]
2KI6NMR-A/F141-268[»]
2LHANMR-A271-422[»]
2N1TNMR-E272-419[»]
2R83X-ray2.70A/B141-422[»]
3F00X-ray1.36A141-266[»]
3F01X-ray1.70A141-266[»]
3F04X-ray1.35A141-266[»]
3F05X-ray1.40A141-266[»]
4ISQX-ray2.65D/E/F33-53[»]
4V11X-ray1.95A273-422[»]
ProteinModelPortaliP21579.
SMRiP21579.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112723. 40 interactors.
DIPiDIP-34042N.
IntActiP21579. 18 interactors.
MINTiMINT-1400342.
STRINGi9606.ENSP00000261205.

Protein family/group databases

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

PTM databases

iPTMnetiP21579.
PhosphoSitePlusiP21579.
SwissPalmiP21579.

Polymorphism and mutation databases

BioMutaiSYT1.
DMDMi135086.

Proteomic databases

EPDiP21579.
PaxDbiP21579.
PeptideAtlasiP21579.
PRIDEiP21579.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261205; ENSP00000261205; ENSG00000067715.
ENST00000393240; ENSP00000376932; ENSG00000067715.
ENST00000552744; ENSP00000447575; ENSG00000067715.
GeneIDi6857.
KEGGihsa:6857.
UCSCiuc001sys.4. human.

Organism-specific databases

CTDi6857.
DisGeNETi6857.
GeneCardsiSYT1.
HGNCiHGNC:11509. SYT1.
HPAiHPA008394.
HPA064788.
MIMi185605. gene.
neXtProtiNX_P21579.
OpenTargetsiENSG00000067715.
PharmGKBiPA36290.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IT3Q. Eukaryota.
ENOG410Z15P. LUCA.
GeneTreeiENSGT00760000118973.
HOGENOMiHOG000232127.
HOVERGENiHBG005010.
InParanoidiP21579.
KOiK15290.
OMAiGEFKVAM.
OrthoDBiEOG091G0XMQ.
PhylomeDBiP21579.
TreeFamiTF315600.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000067715-MONOMER.
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-5250958. Toxicity of botulinum toxin type B (BoNT/B).
R-HSA-5250989. Toxicity of botulinum toxin type G (BoNT/G).
R-HSA-6794361. Interactions of neurexins and neuroligins at synapses.
R-HSA-8856825. Cargo recognition for clathrin-mediated endocytosis.
R-HSA-8856828. Clathrin-mediated endocytosis.
R-HSA-888590. GABA synthesis, release, reuptake and degradation.

Miscellaneous databases

ChiTaRSiSYT1. human.
EvolutionaryTraceiP21579.
GeneWikiiSYT1.
GenomeRNAii6857.
PMAP-CutDBP21579.
PROiP21579.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000067715.
CleanExiHS_SYT1.
ExpressionAtlasiP21579. baseline and differential.
GenevisibleiP21579. HS.

Family and domain databases

Gene3Di2.60.40.150. 2 hits.
InterProiIPR000008. C2_dom.
IPR001565. Synaptotagmin.
IPR015428. Synaptotagmin1.
[Graphical view]
PANTHERiPTHR10024:SF239. PTHR10024:SF239. 1 hit.
PfamiPF00168. C2. 2 hits.
[Graphical view]
PRINTSiPR00360. C2DOMAIN.
PR00399. SYNAPTOTAGMN.
SMARTiSM00239. C2. 2 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 2 hits.
PROSITEiPS50004. C2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSYT1_HUMAN
AccessioniPrimary (citable) accession number: P21579
Secondary accession number(s): Q6AI31
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1991
Last sequence update: May 1, 1991
Last modified: November 2, 2016
This is version 179 of the entry and version 1 of the sequence. [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 12
    Human chromosome 12: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.