P21579 (SYT1_HUMAN) 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
Synonyms:	SVP65, SYT

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	422 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 By similarity.
Subunit structure	Homotetramer Probable. Interacts with SCAMP5, STON2, SV2A, SV2B, SV2C and RIMS1. Forms a complex with SV2B, syntaxin 1 and SNAP25 By similarity. Ref.6
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.
Domain	The first C2 domain mediates Ca2+-dependent phospholipid binding. The second C2 domain mediates interaction with SV2A and STN2 By similarity.
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 Reference proteome
Gene Ontology (GO)
Biological_process	detection of calcium ion Traceable author statement PubMed 11438518. Source: UniProtKB glutamate secretion Traceable author statement. Source: Reactome neurotransmitter secretion Traceable author statement PubMed 11438518. Source: UniProtKB protein homooligomerization Traceable author statement PubMed 11438518. Source: UniProtKB regulation of calcium ion-dependent exocytosis Inferred from electronic annotation. Source: Compara regulation of exocytosis Traceable author statement PubMed 11438518. Source: UniProtKB synaptic vesicle exocytosis Inferred from electronic annotation. Source: Compara
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW chromaffin granule membrane Inferred from electronic annotation. Source: UniProtKB-SubCell clathrin-sculpted acetylcholine transport vesicle membrane Traceable author statement. Source: Reactome clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane Traceable author statement. Source: Reactome clathrin-sculpted glutamate transport vesicle membrane Traceable author statement. Source: Reactome clathrin-sculpted monoamine transport vesicle membrane Traceable author statement. Source: Reactome dense core granule Inferred from electronic annotation. Source: Compara endocytic vesicle membrane Traceable author statement. Source: Reactome excitatory synapse Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuron projection Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement. Source: Reactome presynaptic membrane Inferred from electronic annotation. Source: Compara synaptic vesicle Traceable author statement PubMed 11438518. Source: UniProtKB synaptic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	1-phosphatidylinositol binding Traceable author statement PubMed 11438518. Source: UniProtKB calcium ion binding Inferred from electronic annotation. Source: Compara calcium-dependent phospholipid binding Inferred from electronic annotation. Source: Compara low-density lipoprotein particle receptor binding Inferred from direct assay PubMed 15082773. Source: MGI syntaxin-1 binding Traceable author statement PubMed 11438518. Source: UniProtKB transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CACNB4	O00305-2	2	EBI-524909,EBI-714855
IKBKG	Q9Y6K9	3	EBI-524909,EBI-81279

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 422

422

Synaptotagmin-1

PRO_0000183936

Regions

Topological domain

1 – 57

57

Vesicular Potential

Transmembrane

58 – 80

23

Helical; Potential

Topological domain

81 – 422

342

Cytoplasmic Potential

Domain

157 – 245

89

C2 1

Domain

287 – 378

92

C2 2

Region

136 – 382

247

Phospholipid binding Probable

Sites

Metal binding

172

1

Calcium 2; via carbonyl oxygen By similarity

Metal binding

173

1

Calcium 1 By similarity

Metal binding

173

1

Calcium 2 By similarity

Metal binding

179

1

Calcium 1 By similarity

Metal binding

231

1

Calcium 1 By similarity

Metal binding

231

1

Calcium 2 By similarity

Metal binding

232

1

Calcium 1; via carbonyl oxygen By similarity

Metal binding

233

1

Calcium 1 By similarity

Metal binding

233

1

Calcium 2 By similarity

Metal binding

233

1

Calcium 3 By similarity

Metal binding

236

1

Calcium 3 By similarity

Metal binding

237

1

Calcium 3; via carbonyl oxygen By similarity

Metal binding

239

1

Calcium 2 By similarity

Metal binding

239

1

Calcium 3 By similarity

Amino acid modifications

Modified residue

129

1

Phosphothreonine Ref.7

Modified residue

230

1

Phosphotyrosine By similarity

Modified residue

365

1

Phosphotyrosine By similarity

Modified residue

381

1

Phosphotyrosine By similarity

Lipidation

75

1

S-palmitoyl cysteine By similarity

Lipidation

76

1

S-palmitoyl cysteine By similarity

Lipidation

78

1

S-palmitoyl cysteine By similarity

Lipidation

80

1

S-palmitoyl cysteine By similarity

Lipidation

83

1

S-palmitoyl cysteine By similarity

Glycosylation

25

1

N-linked (GlcNAc...) Potential

Secondary structure

1

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422

Helix Strand Turn

Details...

Beta strand

145 – 153

9

Turn

154 – 157

4

Beta strand

158 – 167

10

Helix

173 – 175

3

Beta strand

180 – 188

9

Beta strand

206 – 213

8

Helix

217 – 220

4

Beta strand

224 – 231

8

Beta strand

234 – 236

3

Beta strand

239 – 247

9

Helix

248 – 250

3

Beta strand

257 – 262

6

Beta strand

276 – 284

9

Turn

285 – 288

4

Beta strand

289 – 299

11

Beta strand

311 – 319

9

Beta strand

322 – 328

7

Beta strand

333 – 337

5

Beta strand

339 – 347

9

Turn

350 – 352

3

Helix

353 – 355

3

Beta strand

356 – 364

9

Beta strand

367 – 369

3

Beta strand

373 – 380

8

Helix

385 – 396

12

Beta strand

402 – 407

6

Helix

411 – 418

8

Sequences

	Sequence		Length	Mass (Da)
	P21579 [UniParc]. Last modified May 1, 1991. Version 1. Checksum: 467F7C58E411AFA9	FASTA	422	47,573
	10 20 30 40 50 60 MVSESHHEAL AAPPVTTVAT VLPSNATEPA SPGEGKEDAF SKLKEKFMNE LHKIPLPPWA 70 80 90 100 110 120 LIAIAIVAVL LVLTCCFCIC KKCLFKKKNK KKGKEKGGKN AINMKDVKDL GKTMKDQALK 130 140 150 160 170 180 DDDAETGLTD GEEKEEPKEE EKLGKLQYSL DYDFQNNQLL VGIIQAAELP ALDMGGTSDP 190 200 210 220 230 240 YVKVFLLPDK KKKFETKVHR KTLNPVFNEQ FTFKVPYSEL GGKTLVMAVY DFDRFSKHDI 250 260 270 280 290 300 IGEFKVPMNT VDFGHVTEEW RDLQSAEKEE QEKLGDICFS LRYVPTAGKL TVVILEAKNL 310 320 330 340 350 360 KKMDVGGLSD PYVKIHLMQN GKRLKKKKTT IKKNTLNPYY NESFSFEVPF EQIQKVQVVV 370 380 390 400 410 420 TVLDYDKIGK NDAIGKVFVG YNSTGAELRH WSDMLANPRR PIAQWHTLQV EEEVDAMLAV KK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structural and functional conservation of synaptotagmin (p65) in Drosophila and humans." Perin M.S., Johnston P.A., Oezcelik T., Jahn R., Francke U., Suedhof T.C. J. Biol. Chem. 266:615-622(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Amygdala and Brain.
[3]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hippocampus.
[4]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: PNS.
[6]	"Human SCAMP5, a novel secretory carrier membrane protein, facilitates calcium-triggered cytokine secretion by interaction with SNARE machinery." Han C., Chen T., Yang M., Li N., Liu H., Cao X. J. Immunol. 182:2986-2996(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SCAMP5.
[7]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-129, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00009439.

PIR

BMHU1Y. A39052.

RefSeq

NP_001129277.1. NM_001135805.1.
NP_001129278.1. NM_001135806.1.
NP_005630.1. NM_005639.2.

UniGene

Hs.310545.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2K45	NMR	-	A	141-268	[»]
2K4A	NMR	-	A	141-268	[»]
2K8M	NMR	-	A/D	141-268	[»]
2KI6	NMR	-	A/F	141-268	[»]
2LHA	NMR	-	A	272-422	[»]
2R83	X-ray	2.70	A/B	141-422	[»]
3F00	X-ray	1.36	A	141-266	[»]
3F01	X-ray	1.70	A	141-266	[»]
3F04	X-ray	1.35	A	141-266	[»]
3F05	X-ray	1.40	A	141-266	[»]

ProteinModelPortal

P21579.

ModBase

Search...

Protein-protein interaction databases

IntAct

P21579. 13 interactions.

MINT

MINT-1400342.

STRING

9606.ENSP00000261205.

PTM databases

PhosphoSite

P21579.

Polymorphism databases

DMDM

135086.

Proteomic databases

PaxDb

P21579.

PRIDE

P21579.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261205; ENSP00000261205; ENSG00000067715.
ENST00000393240; ENSP00000376932; ENSG00000067715.
ENST00000552744; ENSP00000447575; ENSG00000067715.

GeneID

6857.

KEGG

hsa:6857.

UCSC

uc001sys.3. human.

Organism-specific databases

CTD

6857.

GeneCards

GC12P079232.

HGNC

HGNC:11509. SYT1.

HPA

HPA008394.

MIM

185605. gene.

neXtProt

NX_P21579.

PharmGKB

PA36290.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG292488.

HOGENOM

HOG000232127.

HOVERGEN

HBG005010.

InParanoid

P21579.

KO

K15290.

OMA

HDIIGEY.

OrthoDB

EOG4MGS7Q.

PhylomeDB

P21579.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.
REACT_13685. Neuronal System.

Gene expression databases

ArrayExpress

P21579.

Bgee

P21579.

CleanEx

HS_SYT1.

Genevestigator

P21579.

GermOnline

ENSG00000067715. Homo sapiens.

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

ChEMBL

CHEMBL1953.

ChiTaRS

SYT1. human.

EvolutionaryTrace

P21579.

GenomeRNAi

6857.

NextBio

26767.

PMAP-CutDB

P21579.

SOURCE

Search...

Entry information

Entry name

SYT1_HUMAN

Accession

Primary (citable) accession number: P21579
Secondary accession number(s): Q6AI31

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 1, 1991
Last modified:	May 1, 2013
This is version 145 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.