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Protein

Synaptotagmin-7

Gene

Syt7

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Ca2+ sensor involved in Ca2+-dependent exocytosis of secretory and synaptic vesicles through Ca2+ and phospholipid binding to the C2 domain. Ca2+ induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis. SYT7 binds Ca2+ with high affinity and slow kinetics compared to other synaptotagmins (PubMed:26738595). Involved in Ca2+-triggered lysosomal exocytosis, a major component of the plasma membrane repair (By similarity). Ca2+-regulated delivery of lysosomal membranes to the cell surface is also involved in the phagocytic uptake of particles by macrophages (PubMed:16982801, PubMed:21041449). Ca2+-triggered lysosomal exocytosis also plays a role in bone remodeling by regulating secretory pathways in osteoclasts and osteoblasts (PubMed:18539119). Involved in cholesterol transport from lysosome to peroxisome by promoting membrane contacts between lysosomes and peroxisomes: probably acts by promoting vesicle fusion by binding phosphatidylinositol-4,5-bisphosphate on peroxisomal membranes (PubMed:25860611). Acts as a key mediator of synaptic facilitation, a process also named short-term synaptic potentiation: synaptic facilitation takes place at synapses with a low initial release probability and is caused by influx of Ca2+ into the axon terminal after spike generation, increasing the release probability of neurotransmitters (PubMed:24569478, PubMed:26738595). Probably mediates synaptic facilitation by directly increasing the probability of release (PubMed:26738595). May also contribute to synaptic facilitation by regulating synaptic vesicle replenishment, a process required to ensure that synaptic vesicles are ready for the arrival of the next action potential: SYT7 is required for synaptic vesicle replenishment by acting as a sensor for Ca2+ and by forming a complex with calmodulin (PubMed:24569478). Also acts as a regulator of Ca2+-dependent insulin and glucagon secretion in beta-cells (PubMed:18308938, PubMed:19171650). Triggers exocytosis by promoting fusion pore opening and fusion pore expansion in chromaffin cells (PubMed:20956309). Also regulates the secretion of some non-synaptic secretory granules of specialized cells (By similarity).By similarity9 Publications

Cofactori

Ca2+1 PublicationNote: Binds 3 Ca2+ ions per C2 domain.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi166Calcium 1By similarity1
Metal bindingi166Calcium 2By similarity1
Metal bindingi172Calcium 1By similarity1
Metal bindingi225Calcium 11 Publication1
Metal bindingi225Calcium 21 Publication1
Metal bindingi227Calcium 11 Publication1
Metal bindingi227Calcium 21 Publication1
Metal bindingi227Calcium 31 Publication1
Metal bindingi230Calcium 3By similarity1
Metal bindingi233Calcium 21 Publication1
Metal bindingi233Calcium 31 Publication1
Metal bindingi297Calcium 4Combined sources1 Publication1
Metal bindingi297Calcium 5Combined sources1 Publication1
Metal bindingi303Calcium 5Combined sources1 Publication1
Metal bindingi357Calcium 4Combined sources1 Publication1
Metal bindingi357Calcium 5Combined sources1 Publication1
Metal bindingi359Calcium 4Combined sources1 Publication1
Metal bindingi359Calcium 5Combined sources1 Publication1
Metal bindingi359Calcium 6Combined sources1 Publication1
Metal bindingi362Calcium 6Combined sources1 Publication1
Metal bindingi365Calcium 4Combined sources1 Publication1
Metal bindingi365Calcium 6Combined sources1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding
Biological processExocytosis
LigandCalcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Synaptotagmin-7Curated
Alternative name(s):
Synaptotagmin VII1 Publication
Short name:
SytVII1 Publication
Gene namesi
Name:Syt7Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1859545 Syt7

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 16VesicularSequence analysisAdd BLAST16
Transmembranei17 – 37HelicalSequence analysisAdd BLAST21
Topological domaini38 – 403CytoplasmicSequence analysisAdd BLAST366

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasmic vesicle, Lysosome, Membrane, Peroxisome, Synapse

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mice were born at the expected Mendelian ratio and do not show gross abnormalities and/or obvious neurological defects. Mice have a normal life span and are fertile, although reproductive capacity is declining faster with age (PubMed:12925704). Embryonic fibroblasts from Syt7 deficient mice are less susceptible to Trypanosoma cruzi invasion, and display impaired lysosomal exocytosis and resealing after wounding (PubMed:12925704). Mutant mice display impaired insulin secretion: they exhibit normal insulin sensitivity and normal metabolic and Ca2+ responses but impaired insulin release, due to Ca2+-sensing defects (PubMed:18308938). Impaired glucagon secretion (PubMed:19171650). Neurons show enhanced synaptic depression: spontaneous synaptic vesicle release is unaffected, while replenishment is impaired (PubMed:24569478). Abolished synaptic facilitation at all synapses except for mossy fiber synapses, where the remaining enhancement is consistent with use-dependent spike broadening that occurs at this synapse (PubMed:26738595). The loss of facilitation is not due to slowed recovery from depression. The initial probability of release and the presynaptic residual Ca2+ signals are not affected (PubMed:26738595).5 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi35 – 41CGLCHWC → SGLSHWS: Abolishes palmitoylation. Impaired phagocytosis and localization to lysosomes. 1 Publication7
Mutagenesisi225 – 233DYDRFSRND → AYARFSRNA in C2A*; loss of function due to abolished Ca(2+)-binding to the first C2 domain. Impaired ability to mediate synaptic facilitation. 1 Publication9
Mutagenesisi225 – 227DYD → NYN: Loss of Ca(2+)-binding in the first C2 domain. Impaired delivery of lysosomal membrane to nascent phagosomes; when associated with 357-N--N-359. Impaired synaptic vesicle replenishment; when associated with 357-N--N-359. 2 Publications3
Mutagenesisi357 – 359DKD → NKN: Loss of Ca(2+)-binding in the second C2 domain. Impaired delivery of lysosomal membrane to nascent phagosomes; when associated with 225-N--N-227. Impaired synaptic vesicle replenishment; when associated with 225-N--N-227. 2 Publications3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001839581 – 403Synaptotagmin-7Add BLAST403

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52PhosphoserineCombined sources1
Modified residuei58PhosphothreonineCombined sources1
Modified residuei61PhosphoserineCombined sources1
Modified residuei119PhosphoserineBy similarity1
Modified residuei122PhosphoserineCombined sources1
Isoform 4 (identifier: Q9R0N7-4)
Modified residuei169Asymmetric dimethylarginineCombined sources1
Modified residuei171Asymmetric dimethylarginineCombined sources1

Post-translational modificationi

Palmitoylated at its vesicular N-terminus; palmitoylation is required for localization to lysosome and phagocytosis in macrophages.1 Publication

Keywords - PTMi

Lipoprotein, Methylation, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiQ9R0N7
PaxDbiQ9R0N7
PRIDEiQ9R0N7

PTM databases

iPTMnetiQ9R0N7
PhosphoSitePlusiQ9R0N7
SwissPalmiQ9R0N7

Expressioni

Tissue specificityi

Widely expressed. Expressed in insulin-secreting cells (PubMed:18308938). Present in glucagon-secreting cells (at protein level) (PubMed:19171650).2 Publications

Gene expression databases

BgeeiENSMUSG00000024743 Expressed in 231 organ(s), highest expression level in medial dorsal nucleus of thalamus
CleanExiMM_SYT7
GenevisibleiQ9R0N7 MM

Interactioni

Subunit structurei

Homodimer (PubMed:10871604). Can also form heterodimers with SYT6, SYT9 and SYT10 (PubMed:10871604). Interacts with calmodulin (CALM1, CALM2 or CALM3) (PubMed:24569478). Interacts with CD63; required for localization to lysosomes (PubMed:21041449).3 Publications

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9R0N7, 1 interactor
STRINGi10090.ENSMUSP00000127973

Structurei

Secondary structure

1403
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9R0N7
SMRiQ9R0N7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini137 – 239C2 1PROSITE-ProRule annotationAdd BLAST103
Domaini268 – 371C2 2PROSITE-ProRule annotationAdd BLAST104

Domaini

The C2 domains bind Ca2+ and membranes. Binding to membranes involves Ca2+-dependent phospholipid binding. Compared to other members of the family, the C2 domains of SYT7 dock and insert into cellular membranes in response to intracellular Ca2+ concentrations that are lower than those required for other synaptotagmins. The two C2 domains bind independently to planar membranes, without interdomain cooperativity. Moreover, SYT7 C2 domains insert more deeply into membranes compared to other synaptotagmins.By similarity

Sequence similaritiesi

Belongs to the synaptotagmin family.Curated

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IT3N Eukaryota
ENOG410XS7N LUCA
GeneTreeiENSGT00760000118973
HOGENOMiHOG000232126
HOVERGENiHBG005010
InParanoidiQ9R0N7
KOiK19907
OMAiTGEPKCQ
OrthoDBiEOG091G08NG
PhylomeDBiQ9R0N7

Family and domain databases

CDDicd08386 C2A_Synaptotagmin-7, 1 hit
cd08405 C2B_Synaptotagmin-7, 1 hit
Gene3Di2.60.40.150, 2 hits
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR037732 C2A_Synaptotagmin-7
IPR037741 C2B_Synaptotagmin-7
IPR001565 Synaptotagmin
IPR015427 Synaptotagmin7
PANTHERiPTHR10024:SF206 PTHR10024:SF206, 1 hit
PfamiView protein in Pfam
PF00168 C2, 2 hits
PRINTSiPR00360 C2DOMAIN
PR00399 SYNAPTOTAGMN
SMARTiView protein in SMART
SM00239 C2, 2 hits
PROSITEiView protein in PROSITE
PS50004 C2, 2 hits

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 3 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q9R0N7-1) [UniParc]FASTAAdd to basket
Also known as: Synaptotagmin VIIalpha1 Publication, Syt7alphaCurated

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
MYRDPEAASP GAPTRDVLLV SAIITVSLSV TIVLCGLCHW CQRKLGKRYK
60 70 80 90 100
NSLETVGTPD SGRGRGEKKA IKLPAGGKAV NTAPVPGQTP HDESDRRTET
110 120 130 140 150
RSSVSDLVNS LTSEMLMLSP GSEEDEAHEG CSRENLGRIQ FSVGYNFQES
160 170 180 190 200
TLTVKVMKAQ ELPAKDFSGT SDPFVKIYLL PDKKHKLETK VKRKNLNPHW
210 220 230 240 250
NETFLFEGFP YEKVVQRVLY LQVLDYDRFS RNDPIGEVSI PLNKVDLTQM
260 270 280 290 300
QTFWKDLKPC SDGSGSRGEL LLSLCYNPSA NSIIVNIIKA RNLKAMDIGG
310 320 330 340 350
TSDPYVKVWL MYKDKRVEKK KTVTKKRNLN PIFNESFAFD IPTEKLRETT
360 370 380 390 400
IIITVMDKDK LSRNDVIGKI YLSWKSGPGE VKHWKDMIAR PRQPVAQWHQ

LKA
Note: Major isoform.1 Publication
Length:403
Mass (Da):45,472
Last modified:May 1, 2000 - v1
Checksum:i4E63C5779C2ED43E
GO
Isoform 2 (identifier: Q9R0N7-2) [UniParc]FASTAAdd to basket
Also known as: Synaptotagmin VIIgamma1 Publication, Syt7gammaCurated

The sequence of this isoform differs from the canonical sequence as follows:
     72-72: K → NFEDSTLSTA...QNQNAQGDKR

Show »
Length:518
Mass (Da):58,260
Checksum:i98E550CE940B10FA
GO
Isoform 3 (identifier: Q9R0N7-3) [UniParc]FASTAAdd to basket
Also known as: Synaptotagmin VIIbeta1 Publication, Syt7betaCurated

The sequence of this isoform differs from the canonical sequence as follows:
     71-71: I → INDLDRDFWNNNESTVQQKWSSYPPKEFILNISPYAPYGDPRLSL

Show »
Length:447
Mass (Da):50,671
Checksum:iC1968D5EAAEF07B7
GO
Isoform 4 (identifier: Q9R0N7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     72-72: K → NFEDSTLSTA...QNQNAQGDKR

Show »
Length:567
Mass (Da):63,099
Checksum:iF612EDF43F34EB79
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2C9F2C1A0A2C9F2C1_MOUSE
Synaptotagmin-7
Syt7
611Annotation score:
A0A286YCU4A0A286YCU4_MOUSE
Synaptotagmin-7
Syt7
518Annotation score:
A0A286YCR9A0A286YCR9_MOUSE
Synaptotagmin-7
Syt7
224Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05823571I → INDLDRDFWNNNESTVQQKW SSYPPKEFILNISPYAPYGD PRLSL in isoform 3. 1
Alternative sequenceiVSP_05823672K → NFEDSTLSTATTLESIPSSA GEPKCQRPRTLMRQQSLQQP LSQNQRGRQPSQPTTSWDHV VGQIRNRGLDMKSFLEGRMV VLSLVLGLSEQDDFANIPDL QNPGTQQNQNAQGDKR in isoform 2. 1
Alternative sequenceiVSP_05823772K → NFEDSTLSTATTLESIPSSA GEPKCQRPRTLMRQQSLQQP LSQNQQGRQPSQPTTSQSLG QLQAHAASAPGSNPRAYGRG QARQGTSAGSKYRAAGGRSR SNPGSWDHVVGQIRNRGLDM KSFLEGRMVVLSLVLGLSEQ DDFANIPDLQNPGTQQNQNA QGDKR in isoform 4. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB026804 mRNA Translation: BAA85776.1
AB075900 mRNA Translation: BAC44832.1
AB075901 mRNA Translation: BAC44833.1
AC124169 Genomic DNA No translation available.
BC105660 mRNA Translation: AAI05661.1
BC139806 mRNA Translation: AAI39807.1
CCDSiCCDS29575.1 [Q9R0N7-1]
CCDS29576.1 [Q9R0N7-3]
CCDS50388.1 [Q9R0N7-4]
RefSeqiNP_061271.1, NM_018801.3 [Q9R0N7-1]
NP_775090.1, NM_173067.3 [Q9R0N7-3]
NP_775091.2, NM_173068.2 [Q9R0N7-4]
UniGeneiMm.182654

Genome annotation databases

EnsembliENSMUST00000073899; ENSMUSP00000073560; ENSMUSG00000024743 [Q9R0N7-1]
ENSMUST00000169121; ENSMUSP00000127973; ENSMUSG00000024743 [Q9R0N7-4]
ENSMUST00000223586; ENSMUSP00000153482; ENSMUSG00000024743 [Q9R0N7-3]
GeneIDi54525
KEGGimmu:54525
UCSCiuc008gpp.2 mouse
uc008gpq.2 mouse [Q9R0N7-1]
uc012bin.1 mouse

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSYT7_MOUSE
AccessioniPrimary (citable) accession number: Q9R0N7
Secondary accession number(s): A4QPF1
, E9PZA8, Q0D2K7, Q8CF95, Q8CF96
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: May 1, 2000
Last modified: September 12, 2018
This is version 138 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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