Reviewed, UniProtKB/Swiss-Prot P46096 (SYT1_MOUSE)

Names and origin

Protein names

Recommended name:
    Synaptotagmin-1
Alternative name(s):
    Synaptotagmin I
      Short name=SytI
    p65

Gene names

Name:

Syt1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	421 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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, STN2, SV2A, SV2B, SV2C and RIMS1 By similarity. Forms a complex with SV2B, syntaxin 1 and SNAP25.
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 Cytoplasmic vesicle Membrane Synapse
Domain	Repeat Transmembrane
Ligand	Calcium Metal-binding
PTM	Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	neurotransmitter secretion Inferred from direct assay. Source: MGI
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW chromaffin granule membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuron projection Inferred from direct assay. Source: MGI presynaptic membrane Inferred from direct assay. Source: MGI synaptic vesicle membrane Inferred from direct assay. Source: MGI
Molecular function	calcium ion binding Inferred from direct assay. Source: MGI calcium-dependent phospholipid binding Traceable author statement. Source: MGI calcium-dependent protein binding Inferred from physical interaction. Source: HGNC transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Sv2b	Q8JZZ9	1	EBI-445340,EBI-466179

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 421	421	Synaptotagmin-1		PRO_0000183938
Regions
	Topological domain	1 – 57	57	Vesicular Potential
	Transmembrane	58 – 79	22	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 By similarity
	Metal binding	172	1	Calcium 1 By similarity
	Metal binding	172	1	Calcium 2 By similarity
	Metal binding	178	1	Calcium 1 By similarity
	Metal binding	230	1	Calcium 1 By similarity
	Metal binding	230	1	Calcium 2 By similarity
	Metal binding	231	1	Calcium 1; via carbonyl oxygen By similarity
	Metal binding	232	1	Calcium 1 By similarity
	Metal binding	232	1	Calcium 2 By similarity
	Metal binding	232	1	Calcium 3 By similarity
	Metal binding	235	1	Calcium 3 By similarity
	Metal binding	236	1	Calcium 3; via carbonyl oxygen By similarity
	Metal binding	238	1	Calcium 2 By similarity
	Metal binding	238	1	Calcium 3 By similarity
Amino acid modifications
	Modified residue	128	1	Phosphothreonine Ref.7
	Modified residue	229	1	Phosphotyrosine Ref.6
	Modified residue	364	1	Phosphotyrosine Ref.8
	Modified residue	380	1	Phosphotyrosine Ref.6
	Lipidation	74	1	S-palmitoyl cysteine By similarity
	Lipidation	75	1	S-palmitoyl cysteine By similarity
	Lipidation	77	1	S-palmitoyl cysteine By similarity
	Lipidation	79	1	S-palmitoyl cysteine By similarity
	Lipidation	82	1	S-palmitoyl cysteine By similarity
	Glycosylation	24	1	N-linked (GlcNAc...) By similarity

Sequences

	Sequence		Length	Mass (Da)
	P46096-1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 7FDEFF37170BD169	FASTA	421	47,418
	10 20 30 40 50 60 MVSASRPEAL 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

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II." Fukuda M., Aruga J., Niinobe M., Aimoto S., Mikoshiba K. J. Biol. Chem. 269:29206-29211(1994) [PubMed: 7961887] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Testis.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[4]	Lubec G., Kang S.U., Sunyer B., Chen W.-Q. Submitted (JAN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 183-189; 201-233; 245-260; 273-281; 289-297; 302-313; 333-366 AND 376-388, MASS SPECTROMETRY. Strain: C57BL/6 and OF1. Tissue: Brain and Hippocampus.
[5]	"SV2B regulates synaptotagmin 1 by direct interaction." Lazzell D.R., Belizaire R., Thakur P., Sherry D.M., Janz R. J. Biol. Chem. 279:52124-52131(2004) [PubMed: 15466855] [Abstract] Cited for: INTERACTION WITH SV2B; SYNTAXIN-1 AND SNAP25.
[6]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed: 18034455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-229 AND TYR-380, MASS SPECTROMETRY. Tissue: Brain.
[7]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed: 17114649] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-128, MASS SPECTROMETRY. Tissue: Brain cortex.
[8]	Lubec G., Kang S. Submitted (APR-2007) to UniProtKB Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-364, MASS SPECTROMETRY. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	D37792 mRNA. Translation: BAA07040.1. AK078790 mRNA. Translation: BAC37395.1. BC042519 mRNA. Translation: AAH42519.1.
IPI	IPI00129618.
RefSeq	NP_033332.1.
UniGene	Mm.289702
3D structure databases
HSSP	HSSP built from PDB template 1K5W based on UniProtKB P21707.
SMR	P46096. Positions 271-418.
ModBase	Search...
Protein-protein interaction databases
IntAct	P46096. 4 interactions.
Protein family/group databases
TCDB	9.A.48.1.1. unconventional protein secretion (UPS) system.
PTM databases
PhosphoSite	P46096.
Proteomic databases
PRIDE	P46096.
Genome annotation databases
Ensembl	ENSMUSG00000035864. Mus musculus. [Contig view]
GeneID	20979.
KEGG	mmu:20979.
Organism-specific databases
MGI	MGI:99667. Syt1.
Phylogenomic databases
HOGENOM	P46096.
HOVERGEN	P46096.
OMA	P46096. VPHNATE.
Gene expression databases
ArrayExpress	P46096.
Bgee	P46096.
CleanEx	MM_SYT1.
GermOnline	ENSMUSG00000035864. Mus musculus.
Family and domain databases
InterPro	IPR000008. C2_Ca-dep. IPR018029. C2_membr_targeting. IPR001565. Synaptotagmin. IPR015428. Synaptotagmin1_2. [Graphical view]
PANTHER	PTHR10024:SF39. Synaptotagmin1_2. 1 hit.
Pfam	PF00168. C2. 2 hits. [Graphical view]
PRINTS	PR00399. SYNAPTOTAGMN.
SMART	SM00239. C2. 2 hits. [Graphical view]
PROSITE	PS50004. C2. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	299964.
SOURCE	Search...

Entry information

Entry name

SYT1_MOUSE

Accession

Primary (citable) accession number: P46096

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	June 16, 2009
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)