P21707 (SYT1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Synaptotagmin-1

Alternative name(s):
Synaptotagmin I
Short name=SytI
p65

Gene names

Name:

Syt1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	421 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Cofactor	Binds 3 calcium ions per subunit. The ions are bound to the C2 domains.
Subunit structure	Homotetramer Probable. Interacts with SCAMP5 and STON2. Forms a complex with SV2B, syntaxin 1 and SNAP25 By similarity. Interacts with RIMS1. Interacts with SV2A, SV2B and SV2C. Ref.5 Ref.6 Ref.8
Subcellular location	Cytoplasmic vesicle › secretory vesicle › synaptic vesicle membrane; Single-pass membrane protein. Cytoplasmic vesicle › secretory vesicle › chromaffin granule membrane; Single-pass membrane protein. Cytoplasm. Note: Synaptic vesicles and chromaffin granules.
Tissue specificity	Predominantly expressed in rostral, phylogenetically younger brain regions, and in some endocrine tissues.
Domain	The first C2 domain mediates Ca2+-dependent phospholipid binding. Ref.5 The second C2 domain mediates interaction with SV2A and probably with STN2. Ref.5
Sequence similarities	Belongs to the synaptotagmin family. Contains 2 C2 domains.

Ontologies

Keywords
Cellular component	Cell junction Cytoplasm Cytoplasmic vesicle Membrane Synapse
Domain	Repeat Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
PTM	Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	calcium ion-dependent exocytosis Traceable author statement Ref.1. Source: RGD detection of calcium ion Inferred from direct assay PubMed 22229667. Source: RGD positive regulation of calcium ion-dependent exocytosis Inferred from direct assay PubMed 21551071. Source: RGD positive regulation of vesicle fusion Inferred from direct assay PubMed 18508778. Source: RGD synaptic vesicle exocytosis Traceable author statement Ref.1. Source: RGD vesicle docking Inferred from direct assay PubMed 22229667. Source: RGD
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW chromaffin granule membrane Inferred from electronic annotation. Source: UniProtKB-SubCell dense core granule Inferred from direct assay PubMed 22366033. Source: MGI excitatory synapse Inferred from direct assay PubMed 19730411. Source: BHF-UCL integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuron projection Inferred from electronic annotation. Source: Compara plasma membrane Inferred from direct assay PubMed 18179895. Source: BHF-UCL presynaptic membrane Inferred from electronic annotation. Source: Compara synaptic vesicle membrane Traceable author statement Ref.1. Source: RGD
Molecular_function	calcium ion binding Inferred from direct assay PubMed 15340165PubMed 22447935. Source: RGD calcium-dependent phospholipid binding Inferred from direct assay PubMed 7791877. Source: BHF-UCL calcium-dependent protein binding Inferred from direct assay PubMed 22711810. Source: RGD calmodulin binding Inferred from direct assay Ref.1. Source: RGD clathrin binding Inferred from direct assay PubMed 7791877. Source: BHF-UCL phosphatidylinositol-4,5-bisphosphate binding Inferred from direct assay PubMed 22447935. Source: RGD phosphatidylserine binding Inferred from direct assay PubMed 18508778. Source: RGD syntaxin-1 binding Inferred from direct assay PubMed 22711810. Source: RGD transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		4	EBI-458098,EBI-458098
Ap2a2	P18484	5	EBI-458098,EBI-539360
Cacna1b	Q02294	2	EBI-458098,EBI-540038
Scn1b	Q00954	2	EBI-458098,EBI-2619363
Scn2a	P04775	2	EBI-458098,EBI-2619448
STON2	Q8WXE9	2	EBI-458098,EBI-539742	From a different organism.
Sv2a	Q02563	2	EBI-458098,EBI-466194

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 421

421

Synaptotagmin-1

PRO_0000183940

Regions

Topological domain

1 – 57

57

Vesicular Potential

Transmembrane

58 – 79

22

Helical; Potential

Topological domain

80 – 421

342

Cytoplasmic Potential

Domain

143 – 244

102

C2 1

Domain

274 – 377

104

C2 2

Region

135 – 381

247

Phospholipid binding Probable

Compositional bias

80 – 119

40

Lys-rich

Sites

Metal binding

171

1

Calcium 2; via carbonyl oxygen

Metal binding

172

1

Calcium 1

Metal binding

172

1

Calcium 2

Metal binding

178

1

Calcium 1

Metal binding

230

1

Calcium 1

Metal binding

230

1

Calcium 2

Metal binding

231

1

Calcium 1; via carbonyl oxygen

Metal binding

232

1

Calcium 1

Metal binding

232

1

Calcium 2

Metal binding

232

1

Calcium 3

Metal binding

235

1

Calcium 3

Metal binding

236

1

Calcium 3; via carbonyl oxygen

Metal binding

238

1

Calcium 2

Metal binding

238

1

Calcium 3

Amino acid modifications

Modified residue

128

1

Phosphothreonine By similarity

Modified residue

229

1

Phosphotyrosine By similarity

Modified residue

364

1

Phosphotyrosine By similarity

Modified residue

380

1

Phosphotyrosine By similarity

Lipidation

74

1

S-palmitoyl cysteine Ref.7

Lipidation

75

1

S-palmitoyl cysteine Ref.7

Lipidation

77

1

S-palmitoyl cysteine Ref.7

Lipidation

79

1

S-palmitoyl cysteine Ref.7

Lipidation

82

1

S-palmitoyl cysteine Ref.7

Glycosylation

24

1

N-linked (GlcNAc...)

Experimental info

Sequence conflict

188

1

D → E in CAA36981. Ref.1

Sequence conflict

374

1

G → D in CAA36981. Ref.1

Sequence conflict

393

1

M → I in CAA36981. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

421

Helix Strand Turn

Details...

Beta strand

144 – 152

9

Turn

153 – 156

4

Beta strand

157 – 167

11

Beta strand

179 – 186

8

Beta strand

205 – 212

8

Helix

216 – 219

4

Beta strand

223 – 230

8

Beta strand

233 – 235

3

Beta strand

238 – 246

9

Helix

247 – 249

3

Beta strand

256 – 261

6

Beta strand

275 – 283

9

Turn

284 – 287

4

Beta strand

288 – 298

11

Beta strand

310 – 318

9

Beta strand

321 – 327

7

Beta strand

338 – 346

9

Helix

349 – 354

6

Beta strand

356 – 363

8

Beta strand

366 – 368

3

Beta strand

371 – 379

9

Helix

384 – 395

12

Beta strand

396 – 399

4

Beta strand

401 – 406

6

Helix

410 – 417

8

Sequences

	Sequence		Length	Mass (Da)
	P21707 [UniParc]. Last modified May 2, 2006. Version 3. Checksum: 06CE28F04C97A722	FASTA	421	47,399
	10 20 30 40 50 60 MVSASHPEAL AAPVTTVATL VPHNATEPAS PGEGKEDAFS KLKQKFMNEL HKIPLPPWAL 70 80 90 100 110 120 IAIAIVAVLL VVTCCFCVCK KCLFKKKNKK KGKEKGGKNA INMKDVKDLG KTMKDQALKD 130 140 150 160 170 180 DDAETGLTDG EEKEEPKEEE KLGKLQYSLD YDFQNNQLLV GIIQAAELPA LDMGGTSDPY 190 200 210 220 230 240 VKVFLLPDKK KKFETKVHRK TLNPVFNEQF TFKVPYSELG GKTLVMAVYD FDRFSKHDII 250 260 270 280 290 300 GEFKVPMNTV DFGHVTEEWR DLQSAEKEEQ EKLGDICFSL RYVPTAGKLT VVILEAKNLK 310 320 330 340 350 360 KMDVGGLSDP YVKIHLMQNG KRLKKKKTTI KKNTLNPYYN ESFSFEVPFE QIQKVQVVVT 370 380 390 400 410 420 VLDYDKIGKN DAIGKVFVGY NSTGAELRHW SDMLANPRRP IAQWHTLQVE EEVDAMLAVK K

References

[1]	"Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C." Perin M.S., Fried V.A., Mignery G.A., Jahn R., Suedhof T.C. Nature 345:260-263(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Synaptotagmin gene content of the sequenced genomes." Craxton M.A. BMC Genomics 5:43-43(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Functional analysis of synaptotagmin." Sunitha S.S., Thekkuveettil A. Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE. Strain: Wistar.
[4]	Lubec G., Chen W.-Q. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 214-233; 289-297; 355-366 AND 376-388, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Hippocampus.
[5]	"Isoform-specific, calcium-regulated interaction of the synaptic vesicle proteins SV2 and synaptotagmin." Schivell A.E., Batchelor R.H., Bajjalieh S.M. J. Biol. Chem. 271:27770-27775(1996) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SV2A, DOMAIN.
[6]	"Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin." Coppola T., Magnin-Luethi S., Perret-Menoud V., Gattesco S., Schiavo G., Regazzi R. J. Biol. Chem. 276:32756-32762(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RIMS1. Tissue: Brain.
[7]	"Palmitoylation sites and processing of synaptotagmin I, the putative calcium sensor for neurosecretion." Heindel U., Schmidt M.F., Veit M. FEBS Lett. 544:57-62(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PALMITOYLATION AT CYS-74; CYS-75; CYS-77; CYS-79 AND CYS-82.
[8]	"SV2A and SV2C contain a unique synaptotagmin-binding site." Schivell A.E., Mochida S., Kensel-Hammes P., Custer K.L., Bajjalieh S.M. Mol. Cell. Neurosci. 29:56-64(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SV2A; SV2B AND SV2C.
[9]	"Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold." Sutton R.B., Davletov B.A., Berghuis A.M., Suedhof T.C., Sprang S.R. Cell 80:929-938(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 132-266.
[10]	"Solution structures of the Ca2+-free and Ca2+-bound C2A domain of synaptotagmin I: does Ca2+ induce a conformational change?" Shao X., Fernandez I., Suedhof T.C., Rizo J. Biochemistry 37:16106-16115(1998) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 140-267.
[11]	"Three-dimensional structure of the synaptotagmin 1 C2B-domain: synaptotagmin 1 as a phospholipid binding machine." Fernandez I., Arac D., Ubach J., Gerber S.H., Shin O., Gao Y., Anderson R.G., Suedhof T.C., Rizo J. Neuron 32:1057-1069(2001) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 270-421.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X52772 mRNA. Translation: CAA36981.1.
AJ617615 mRNA. Translation: CAE85101.1.
DQ181550 mRNA. Translation: ABA00482.1.

IPI

IPI00206170.

PIR

S09595.

RefSeq

NP_001028852.2. NM_001033680.2.

UniGene

Rn.216272.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BYN	NMR	-	A	140-267	[»]
1K5W	NMR	-	A	270-421	[»]
1RSY	X-ray	1.90	A	132-266	[»]
1TJM	X-ray	1.18	A	271-421	[»]
1TJX	X-ray	1.04	A	271-421	[»]
1UOV	X-ray	1.65	A	271-421	[»]
1UOW	X-ray	1.04	A	271-421	[»]

ProteinModelPortal

P21707.

SMR

P21707. Positions 140-418.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29064N.

IntAct

P21707. 15 interactions.

MINT

MINT-4542559.

PTM databases

PhosphoSite

P21707.

Proteomic databases

PaxDb

P21707.

PRIDE

P21707.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000048880; ENSRNOP00000049624; ENSRNOG00000006426.

GeneID

25716.

KEGG

rno:25716.

UCSC

RGD:3803. rat.

Organism-specific databases

CTD

6857.

RGD

3803. Syt1.

Phylogenomic databases

eggNOG

COG5038.

GeneTree

ENSGT00620000087641.

HOGENOM

HOG000232127.

HOVERGEN

HBG005010.

InParanoid

P21707.

KO

K15290.

OMA

HDIIGEY.

OrthoDB

EOG4MGS7Q.

Gene expression databases

ArrayExpress

P21707.

Genevestigator

P21707.

GermOnline

ENSRNOG00000006426. Rattus norvegicus.

Family and domain databases

InterPro

IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR020477. C2_dom.
IPR018029. C2_membr_targeting.
IPR001565. Synaptotagmin.
IPR015428. Synaptotagmin1.
[Graphical view]

PANTHER

PTHR10024:SF39. PTHR10024:SF39. 1 hit.

Pfam

PF00168. C2. 2 hits.
[Graphical view]

PRINTS

PR00360. C2DOMAIN.
PR00399. SYNAPTOTAGMN.

SMART

SM00239. C2. 2 hits.
[Graphical view]

SUPFAM

SSF49562. C2_CaLB. 2 hits.

PROSITE

PS50004. C2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P21707.

NextBio

607797.

Entry information

Entry name

SYT1_RAT

Accession

Primary (citable) accession number: P21707
Secondary accession number(s): Q3S2E6, Q707P5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 2, 2006
Last modified:	May 1, 2013
This is version 139 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program