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Protein

Synaptotagmin-7

Gene

SYT7

Organism
Homo sapiens (Human)
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 (By similarity). Ca2+ induces binding of the C2-domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis (By similarity). SYT7 binds Ca2+ with high affinity and slow kinetics compared to other synaptotagmins (By similarity). Involved in Ca2+-triggered lysosomal exocytosis, a major component of the plasma membrane repair (PubMed:11342594). Ca2+-regulated delivery of lysosomal membranes to the cell surface is also involved in the phagocytic uptake of particles by macrophages (By similarity). Ca2+-triggered lysosomal exocytosis also plays a role in bone remodeling by regulating secretory pathways in osteoclasts and osteoblasts (By similarity). In case of infection, involved in participates cell invasion by Trypanosoma cruzi via Ca2+-triggered lysosomal exocytosis (PubMed:11342594, PubMed:15811535). 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 (By similarity). 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 (By similarity). Probably mediates synaptic facilitation by directly increasing the probability of release (By similarity). 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 (By similarity). Also acts as a regulator of Ca2+-dependent insulin and glucagon secretion in beta-cells (By similarity). Triggers exocytosis by promoting fusion pore opening and fusion pore expansion in chromaffin cells (By similarity). Also regulates the secretion of some non-synaptic secretory granules of specialized cells (By similarity).By similarity2 Publications

Cofactori

Ca2+By similarityNote: Binds 3 Ca2+ ions per C2 domain.By similarity

Sites

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding
Biological processExocytosis
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-6794361 Neurexins and neuroligins

Names & Taxonomyi

Protein namesi
Recommended name:
Synaptotagmin-7Curated
Alternative name(s):
IPCA-7
Prostate cancer-associated protein 7
Synaptotagmin VII
Short name:
SytVII
Gene namesi
Name:SYT7Imported
Synonyms:PCANAP7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000011347.9
HGNCiHGNC:11514 SYT7
MIMi604146 gene
neXtProtiNX_O43581

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

Organism-specific databases

OpenTargetsiENSG00000011347
PharmGKBiPA36295

Polymorphism and mutation databases

BioMutaiSYT7

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001839571 – 403Synaptotagmin-7Add BLAST403

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52PhosphoserineBy similarity1
Modified residuei58PhosphothreonineBy similarity1
Modified residuei61PhosphoserineBy similarity1
Modified residuei119PhosphoserineBy similarity1
Modified residuei122PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiO43581
PaxDbiO43581
PeptideAtlasiO43581
PRIDEiO43581
ProteomicsDBi49062

PTM databases

iPTMnetiO43581
PhosphoSitePlusiO43581
SwissPalmiO43581

Expressioni

Tissue specificityi

Expressed in a variety of adult and fetal tissues.

Gene expression databases

BgeeiENSG00000011347
CleanExiHS_SYT7
ExpressionAtlasiO43581 baseline and differential
GenevisibleiO43581 HS

Organism-specific databases

HPAiHPA012869

Interactioni

Subunit structurei

Homodimer. Can also form heterodimers with SYT6, SYT9 and SYT10. Interacts with calmodulin (CALM1, CALM2 or CALM3). Interacts with CD63; required for localization to lysosomes.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
SIAH1Q8IUQ43EBI-10184345,EBI-747107

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114525, 4 interactors
ELMiO43581
IntActiO43581, 1 interactor
STRINGi9606.ENSP00000263846

Structurei

Secondary structure

1403
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi138 – 145Combined sources8
Beta strandi147 – 149Combined sources3
Beta strandi152 – 161Combined sources10
Beta strandi166 – 169Combined sources4
Beta strandi173 – 181Combined sources9
Beta strandi184 – 188Combined sources5
Beta strandi202 – 206Combined sources5
Helixi211 – 214Combined sources4
Beta strandi217 – 225Combined sources9
Beta strandi228 – 231Combined sources4
Beta strandi233 – 241Combined sources9
Turni242 – 244Combined sources3
Beta strandi251 – 255Combined sources5

3D structure databases

ProteinModelPortaliO43581
SMRiO43581
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43581

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 (PubMed:22966849). The two C2 domains bind independently to planar membranes, without interdomain cooperativity (PubMed:25437758). Moreover, SYT7 C2 domains insert more deeply into membranes compared to other synaptotagmins (PubMed:26322740, PubMed:26333120).4 Publications

Sequence similaritiesi

Belongs to the synaptotagmin family.Curated

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1028 Eukaryota
ENOG410XRME LUCA
GeneTreeiENSGT00760000118973
HOGENOMiHOG000232126
HOVERGENiHBG005010
InParanoidiO43581
KOiK19907
OMAiTGEPKCQ
OrthoDBiEOG091G08NG
PhylomeDBiO43581
TreeFamiTF315600

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 (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43581-1) [UniParc]FASTAAdd to basket

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

LKA
Note: Major isoform.1 Publication
Length:403
Mass (Da):45,501
Last modified:September 23, 2008 - v3
Checksum:iC9BFB26D298EDBE4
GO
Isoform 2 (identifier: O43581-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:478
Mass (Da):52,821
Checksum:i6F6B1DD2C9AFF15F
GO
Isoform 3 (identifier: O43581-3) [UniParc]FASTAAdd to basket

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

Show »
Length:686
Mass (Da):75,797
Checksum:i96C75AAD8D9CCBFB
GO
Isoform 4 (identifier: O43581-4) [UniParc]FASTAAdd to basket

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

Show »
Length:611
Mass (Da):68,478
Checksum:i68702B2463439DB6
GO
Isoform 5 (identifier: O43581-5) [UniParc]FASTAAdd to basket

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

Show »
Length:522
Mass (Da):58,019
Checksum:iDFA24AF0D17AD221
GO
Isoform 6 (identifier: O43581-6) [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):50,700
Checksum:i70A51A39F51AFB7F
GO

Sequence cautioni

The sequence AAB92667 differs from that shown. Reason: Frameshift at positions 6, 10 and 15.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti154V → L in AAB92667 (PubMed:9615227).Curated1
Sequence conflicti188E → K in AAB92667 (PubMed:9615227).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052241332I → N1 PublicationCorresponds to variant dbSNP:rs407740Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04599171I → INGTLLSGAKVAAAAGLAVE REGRLGEKPAPVPPPGEDAL RSGGAAPSEPGSGGKAGRGR WRTVQSHLAAGKLNLS in isoform 2. 1 Publication1
Alternative sequenceiVSP_05823171I → INDLDRDFWNNNESTVQQKW SSYPPKEFILNISPYAPYGD PRLSLNGTLLSGAKVAAAAG LAVEREGRLGEKPAPVPPPG EDALRSGGAAPSEPGSGGKA GRGRWRTVQSHLAAGKLNLS in isoform 5. 1
Alternative sequenceiVSP_05823271I → INDLDRDFWNNNESTVQQKW SSYPPKEFILNISPYAPYGD PRLSL in isoform 6. 1
Alternative sequenceiVSP_05823372K → NDLDRDFWNNNESTVQQKWS SYPPKEFILNISPYAPYGDP RLSLNGTLLSGAKVAAAAGL AVEREGRLGEKPAPVPPPGE DALRSGGAAPSEPGSGGKAG RGRWRTVQSHLAAGKLNLSN FEDSTLSTATTLESIPSSTG EPKCQRPRTLMRQQSLQQPL SQHQRGRQPSQPTTSQSLGQ LQAHMASAPGPNPRAYGRGQ ARQGTSAGSKYRAAGGRSRS NPGSWDHVVGQIRNRGLDMK SFLEGRMVVLSLVLGLSEQD DFANIPDLQNPGTQQNQNAQ GDKR in isoform 3. 1
Alternative sequenceiVSP_05823472K → NDLDRDFWNNNESTVQQKWS SYPPKEFILNISPYAPYGDP RLSLNFEDSTLSTATTLESI PSSTGEPKCQRPRTLMRQQS LQQPLSQHQRGRQPSQPTTS QSLGQLQAHMASAPGPNPRA YGRGQARQGTSAGSKYRAAG GRSRSNPGSWDHVVGQIRNR GLDMKSFLEGRMVVLSLVLG LSEQDDFANIPDLQNPGTQQ NQNAQGDKR in isoform 4. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF038535 mRNA Translation: AAB92667.1 Frameshift.
AP002754 Genomic DNA No translation available.
AP003108 Genomic DNA No translation available.
AP003559 Genomic DNA No translation available.
CH471076 Genomic DNA Translation: EAW73956.1
BC125170 mRNA Translation: AAI25171.1
BC125171 mRNA No translation available.
CCDSiCCDS31577.1 [O43581-1]
CCDS58139.1 [O43581-2]
CCDS73298.1 [O43581-6]
RefSeqiNP_001238994.1, NM_001252065.1 [O43581-2]
NP_001287702.1, NM_001300773.1 [O43581-6]
NP_004191.2, NM_004200.3 [O43581-1]
XP_005274440.1, XM_005274383.4 [O43581-3]
XP_005274442.1, XM_005274385.4 [O43581-4]
UniGeneiHs.131188
Hs.684589

Genome annotation databases

EnsembliENST00000263846; ENSP00000263846; ENSG00000011347 [O43581-1]
ENST00000535826; ENSP00000437720; ENSG00000011347 [O43581-5]
ENST00000539008; ENSP00000439694; ENSG00000011347 [O43581-3]
ENST00000540677; ENSP00000444201; ENSG00000011347 [O43581-2]
ENST00000542670; ENSP00000444019; ENSG00000011347 [O43581-4]
ENST00000542836; ENSP00000444568; ENSG00000011347 [O43581-6]
GeneIDi9066
KEGGihsa:9066
UCSCiuc001nrv.4 human [O43581-1]
uc001nrx.2 human
uc058cdk.1 human
uc058cdl.1 human
uc058cdm.1 human

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSYT7_HUMAN
AccessioniPrimary (citable) accession number: O43581
Secondary accession number(s): F5GZC2
, F5GZU9, F5H126, F5H1N2, F5H6C1, Q08AH6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 18, 2001
Last sequence update: September 23, 2008
Last modified: June 20, 2018
This is version 162 of the entry and version 3 of the sequence. See 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 11
    Human chromosome 11: 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

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