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Protein

Extended synaptotagmin-1

Gene

ESYT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport (By similarity). Binds calcium (via the C2 domains) and translocates to sites of contact between the endoplasmic reticulum and the cell membrane in response to increased cytosolic calcium levels. Helps tether the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane.By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi344Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi345Calcium 1By similarity1
Metal bindingi345Calcium 2By similarity1
Metal bindingi357Calcium 2By similarity1
Metal bindingi404Calcium 1By similarity1
Metal bindingi404Calcium 2By similarity1
Metal bindingi406Calcium 1By similarity1
Metal bindingi406Calcium 2By similarity1
Metal bindingi406Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi408Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi410Calcium 3By similarity1
Metal bindingi411Calcium 1By similarity1

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • lipid binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Biological processLipid transport, Transport
LigandCalcium, Lipid-binding, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-1660662 Glycosphingolipid metabolism

Protein family/group databases

TCDBi9.A.57.1.1 the extended-synaptotagmin (e-syt) family

Names & Taxonomyi

Protein namesi
Recommended name:
Extended synaptotagmin-1
Short name:
E-Syt1
Alternative name(s):
Membrane-bound C2 domain-containing protein
Gene namesi
Name:ESYT1
Synonyms:FAM62A, KIAA0747, MBC2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000139641.12
HGNCiHGNC:29534 ESYT1
neXtProtiNX_Q9BSJ8

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 – 38CytoplasmicSequence analysisAdd BLAST38
Transmembranei39 – 59HelicalSequence analysisAdd BLAST21
Topological domaini60 – 62LumenalSequence analysis3
Transmembranei63 – 83HelicalSequence analysisAdd BLAST21
Topological domaini84 – 1104CytoplasmicSequence analysisAdd BLAST1021

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi406D → A: No effect on translocation to sites of contact between the endoplasmic reticulum and the cell membrane. 1 Publication1
Mutagenesisi663D → A: Abolishes location at the cell membrane; when associated with A-675 and 722-A--A-729. 1 Publication1
Mutagenesisi675D → A: Abolishes location at the cell membrane; when associated with A-675 and 722-A--A-729. 1 Publication1
Mutagenesisi722 – 729DKDLDKDD → AKALAKAA: Abolishes location at the cell membrane; when associated with A-663 and A-675. 1 Publication8
Mutagenesisi724D → A: Loss of translocation to sites of contact between the endoplasmic reticulum and the cell membrane. 1 Publication1

Organism-specific databases

DisGeNETi23344
OpenTargetsiENSG00000139641
PharmGKBiPA165512688

Chemistry databases

ChEMBLiCHEMBL3621033

Polymorphism and mutation databases

BioMutaiESYT1
DMDMi74733019

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002343441 – 1104Extended synaptotagmin-1Add BLAST1104

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei324Phosphoserine; by CDK5By similarity1
Modified residuei817N6-acetyllysineCombined sources1
Modified residuei820PhosphoserineCombined sources1
Modified residuei941PhosphoserineCombined sources1
Modified residuei948PhosphothreonineCombined sources1
Modified residuei949PhosphoserineCombined sources1
Modified residuei963PhosphoserineCombined sources1
Modified residuei1009PhosphotyrosineBy similarity1
Modified residuei1034PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on Ser residues in insulin-treated adipocytes (in vitro); this promotes interaction with SLC2A4.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9BSJ8
MaxQBiQ9BSJ8
PaxDbiQ9BSJ8
PeptideAtlasiQ9BSJ8
PRIDEiQ9BSJ8
ProteomicsDBi78906
78907 [Q9BSJ8-2]

2D gel databases

OGPiQ9Y416

PTM databases

iPTMnetiQ9BSJ8
PhosphoSitePlusiQ9BSJ8
SwissPalmiQ9BSJ8

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiENSG00000139641 Expressed in 237 organ(s), highest expression level in vagina
CleanExiHS_FAM62A
ExpressionAtlasiQ9BSJ8 baseline and differential
GenevisibleiQ9BSJ8 HS

Organism-specific databases

HPAiHPA016858
HPA076926

Interactioni

Subunit structurei

Interacts (phosphorylated form) with SLC2A4 (By similarity). Interacts with ESYT2 and ESYT3.By similarity1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116927, 50 interactors
DIPiDIP-57197N
ELMiQ9BSJ8
IntActiQ9BSJ8, 27 interactors
MINTiQ9BSJ8
STRINGi9606.ENSP00000267113

Structurei

3D structure databases

ProteinModelPortaliQ9BSJ8
SMRiQ9BSJ8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini135 – 313SMP-LTDPROSITE-ProRule annotationAdd BLAST179
Domaini316 – 417C2 1PROSITE-ProRule annotationAdd BLAST102
Domaini465 – 558C2 2PROSITE-ProRule annotationAdd BLAST94
Domaini634 – 735C2 3PROSITE-ProRule annotationAdd BLAST102
Domaini785 – 877C2 4PROSITE-ProRule annotationAdd BLAST93
Domaini972 – 1077C2 5PROSITE-ProRule annotationAdd BLAST106

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1018 – 1025Required for phosphatidylinositol 4,5-bisphosphate-dependent location at the cell membraneBy similarity8

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili91 – 116Sequence analysisAdd BLAST26

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi924 – 935Poly-SerAdd BLAST12
Compositional biasi1012 – 1015Poly-Leu4

Domaini

Anchored to the endoplasmic reticulum membrane by a transmembrane hairpin structure; both N-terminus and C-terminus are cytoplasmic.1 Publication
The C2 domains mediate lipid and calcium binding. The N-terminal C2 domain binds calcium ions and is important for calcium-dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium (By similarity). The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for translocation to the cell membrane in response to increased cytosolic calcium levels (PubMed:24183667 and PubMed:23791178).By similarity
The SMP-LTD domain is a barrel-like domain that can bind various types of glycerophospholipids in its interior (By similarity).By similarity

Sequence similaritiesi

Belongs to the extended synaptotagmin family.Curated

Keywords - Domaini

Coiled coil, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410ISCC Eukaryota
ENOG410XPR4 LUCA
GeneTreeiENSGT00550000074417
HOVERGENiHBG055795
InParanoidiQ9BSJ8
OMAiGVEAHSH
PhylomeDBiQ9BSJ8
TreeFamiTF324255

Family and domain databases

CDDicd08391 C2A_C2C_Synaptotagmin_like, 2 hits
cd04050 C2B_Synaptotagmin-like, 2 hits
cd04030 C2C_KIAA1228, 1 hit
Gene3Di2.60.40.150, 5 hits
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR037752 C2C_KIAA1228
IPR037733 Ext_Synaptotagmin_C2A
IPR037749 Ext_Synaptotagmin_C2B
IPR031468 SMP_LBD
IPR039010 Synaptotagmin_SMP
PfamiView protein in Pfam
PF00168 C2, 5 hits
PF17047 SMP_LBD, 1 hit
PRINTSiPR00360 C2DOMAIN
SMARTiView protein in SMART
SM00239 C2, 5 hits
PROSITEiView protein in PROSITE
PS50004 C2, 5 hits
PS51847 SMP, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.iShow all

Isoform 1 (identifier: Q9BSJ8-1) [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
MERSPGEGPS PSPMDQPSAP SDPTDQPPAA HAKPDPGSGG QPAGPGAAGE
60 70 80 90 100
ALAVLTSFGR RLLVLIPVYL AGAVGLSVGF VLFGLALYLG WRRVRDEKER
110 120 130 140 150
SLRAARQLLD DEEQLTAKTL YMSHRELPAW VSFPDVEKAE WLNKIVAQVW
160 170 180 190 200
PFLGQYMEKL LAETVAPAVR GSNPHLQTFT FTRVELGEKP LRIIGVKVHP
210 220 230 240 250
GQRKEQILLD LNISYVGDVQ IDVEVKKYFC KAGVKGMQLH GVLRVILEPL
260 270 280 290 300
IGDLPFVGAV SMFFIRRPTL DINWTGMTNL LDIPGLSSLS DTMIMDSIAA
310 320 330 340 350
FLVLPNRLLV PLVPDLQDVA QLRSPLPRGI IRIHLLAARG LSSKDKYVKG
360 370 380 390 400
LIEGKSDPYA LVRLGTQTFC SRVIDEELNP QWGETYEVMV HEVPGQEIEV
410 420 430 440 450
EVFDKDPDKD DFLGRMKLDV GKVLQASVLD DWFPLQGGQG QVHLRLEWLS
460 470 480 490 500
LLSDAEKLEQ VLQWNWGVSS RPDPPSAAIL VVYLDRAQDL PLKKGNKEPN
510 520 530 540 550
PMVQLSIQDV TQESKAVYST NCPVWEEAFR FFLQDPQSQE LDVQVKDDSR
560 570 580 590 600
ALTLGALTLP LARLLTAPEL ILDQWFQLSS SGPNSRLYMK LVMRILYLDS
610 620 630 640 650
SEICFPTVPG CPGAWDVDSE NPQRGSSVDA PPRPCHTTPD SQFGTEHVLR
660 670 680 690 700
IHVLEAQDLI AKDRFLGGLV KGKSDPYVKL KLAGRSFRSH VVREDLNPRW
710 720 730 740 750
NEVFEVIVTS VPGQELEVEV FDKDLDKDDF LGRCKVRLTT VLNSGFLDEW
760 770 780 790 800
LTLEDVPSGR LHLRLERLTP RPTAAELEEV LQVNSLIQTQ KSAELAAALL
810 820 830 840 850
SIYMERAEDL PLRKGTKHLS PYATLTVGDS SHKTKTISQT SAPVWDESAS
860 870 880 890 900
FLIRKPHTES LELQVRGEGT GVLGSLSLPL SELLVADQLC LDRWFTLSSG
910 920 930 940 950
QGQVLLRAQL GILVSQHSGV EAHSHSYSHS SSSLSEEPEL SGGPPHITSS
960 970 980 990 1000
APELRQRLTH VDSPLEAPAG PLGQVKLTLW YYSEERKLVS IVHGCRSLRQ
1010 1020 1030 1040 1050
NGRDPPDPYV SLLLLPDKNR GTKRRTSQKK RTLSPEFNER FEWELPLDEA
1060 1070 1080 1090 1100
QRRKLDVSVK SNSSFMSRER ELLGKVQLDL AETDLSQGVA RWYDLMDNKD

KGSS
Length:1,104
Mass (Da):122,856
Last modified:June 1, 2001 - v1
Checksum:iE72B20C458B96F19
GO
Isoform 2 (identifier: Q9BSJ8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     491-491: P → PMVTSELYPPQ

Note: No experimental confirmation available.
Show »
Length:1,114
Mass (Da):124,003
Checksum:i3ECE7EC47B8A90A8
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8VZB1F8VZB1_HUMAN
Extended synaptotagmin-1
ESYT1
88Annotation score:

Sequence cautioni

The sequence BAB15139 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAB15268 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti133F → L in BAF83026 (PubMed:14702039).Curated1
Sequence conflicti489D → N in BAB15139 (PubMed:14702039).Curated1
Sequence conflicti738L → F in BAB15139 (PubMed:14702039).Curated1
Sequence conflicti785S → R in BAF83026 (PubMed:14702039).Curated1
Sequence conflicti998L → P in BAB15139 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_038190764R → C. Corresponds to variant dbSNP:rs35075600Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_018277491P → PMVTSELYPPQ in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ993200 mRNA Translation: ABJ97705.1
AK025463 mRNA Translation: BAB15139.1 Different initiation.
AK025878 mRNA Translation: BAB15268.1 Different initiation.
AK290337 mRNA Translation: BAF83026.1
CH471054 Genomic DNA Translation: EAW96891.1
BC004998 mRNA Translation: AAH04998.1
AB018290 mRNA Translation: BAA34467.1
AL050134 mRNA Translation: CAB43284.1
CCDSiCCDS53801.1 [Q9BSJ8-2]
CCDS8904.1 [Q9BSJ8-1]
PIRiT08769
T13156
RefSeqiNP_001171725.1, NM_001184796.1 [Q9BSJ8-2]
NP_056107.1, NM_015292.2 [Q9BSJ8-1]
UniGeneiHs.632729

Genome annotation databases

EnsembliENST00000267113; ENSP00000267113; ENSG00000139641 [Q9BSJ8-2]
ENST00000394048; ENSP00000377612; ENSG00000139641 [Q9BSJ8-1]
GeneIDi23344
KEGGihsa:23344
UCSCiuc001sjq.4 human [Q9BSJ8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiESYT1_HUMAN
AccessioniPrimary (citable) accession number: Q9BSJ8
Secondary accession number(s): A0FGR7
, A8K2S2, O94848, Q6PJN4, Q9H6J1, Q9H6W2, Q9Y416
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: June 1, 2001
Last modified: September 12, 2018
This is version 153 of the entry and version 1 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

Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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