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Protein

Extended synaptotagmin-3

Gene

ESYT3

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). Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane.By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi321Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi322Calcium 1By similarity1
Metal bindingi322Calcium 2By similarity1
Metal bindingi332Calcium 2By similarity1
Metal bindingi379Calcium 1By similarity1
Metal bindingi379Calcium 2By similarity1
Metal bindingi380Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi381Calcium 1By similarity1
Metal bindingi381Calcium 2By similarity1
Metal bindingi381Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi383Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi385Calcium 3By similarity1
Metal bindingi386Calcium 1By similarity1

GO - Molecular functioni

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.57.1.3 the extended-synaptotagmin (e-syt) family

Names & Taxonomyi

Protein namesi
Recommended name:
Extended synaptotagmin-3
Short name:
E-Syt3
Alternative name(s):
Chr3Syt
Gene namesi
Name:ESYT3
Synonyms:FAM62C
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000158220.13
HGNCiHGNC:24295 ESYT3
neXtProtiNX_A0FGR9

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 – 29CytoplasmicSequence analysisAdd BLAST29
Transmembranei30 – 50HelicalSequence analysisAdd BLAST21
Transmembranei51 – 71HelicalSequence analysisAdd BLAST21
Topological domaini72 – 886CytoplasmicSequence analysisAdd BLAST815

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi83850
OpenTargetsiENSG00000158220
PharmGKBiPA165697118

Polymorphism and mutation databases

BioMutaiESYT3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003148991 – 886Extended synaptotagmin-3Add BLAST886

Proteomic databases

PaxDbiA0FGR9
PRIDEiA0FGR9

PTM databases

iPTMnetiA0FGR9
PhosphoSitePlusiA0FGR9

Expressioni

Tissue specificityi

Widely expressed with high level in cerebellum and skin.1 Publication

Gene expression databases

BgeeiENSG00000158220
CleanExiHS_FAM62C
ExpressionAtlasiA0FGR9 baseline and differential
GenevisibleiA0FGR9 HS

Organism-specific databases

HPAiHPA039200

Interactioni

Subunit structurei

Interacts with ESYT1 and ESYT2.1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi123766, 1 interactor
DIPiDIP-61998N
IntActiA0FGR9, 2 interactors
STRINGi9606.ENSP00000374218

Structurei

3D structure databases

ProteinModelPortaliA0FGR9
SMRiA0FGR9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini114 – 291SMP-LTDPROSITE-ProRule annotationAdd BLAST178
Domaini293 – 392C2 1PROSITE-ProRule annotationAdd BLAST100
Domaini430 – 544C2 2PROSITE-ProRule annotationAdd BLAST115
Domaini756 – 860C2 3PROSITE-ProRule annotationAdd BLAST105

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni801 – 808Required for phosphatidylinositol 4,5-bisphosphate-dependent location at the cell membraneBy similarity8

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 location at the cell membrane (PubMed:23791178).By similarity1 Publication
The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior (By similarity).By similarity

Sequence similaritiesi

Belongs to the extended synaptotagmin family.Curated

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1012 Eukaryota
ENOG410YCXU LUCA
GeneTreeiENSGT00550000074417
HOGENOMiHOG000043080
HOVERGENiHBG055795
InParanoidiA0FGR9
OMAiAWPPKRL
OrthoDBiEOG091G02X7
PhylomeDBiA0FGR9
TreeFamiTF324255

Family and domain databases

CDDicd08391 C2A_C2C_Synaptotagmin_like, 1 hit
cd04050 C2B_Synaptotagmin-like, 1 hit
cd04030 C2C_KIAA1228, 1 hit
Gene3Di2.60.40.150, 3 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
PfamiView protein in Pfam
PF00168 C2, 3 hits
PF17047 SMP_LBD, 1 hit
PRINTSiPR00360 C2DOMAIN
SMARTiView protein in SMART
SM00239 C2, 3 hits
PROSITEiView protein in PROSITE
PS50004 C2, 3 hits
PS51847 SMP, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: A0FGR9-1) [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
MRAEEPCAPG APSALGAQRT PGPELRLSSQ LLPELCTFVV RVLFYLGPVY
60 70 80 90 100
LAGYLGLSIT WLLLGALLWM WWRRNRRGKL GRLAAAFEFL DNEREFISRE
110 120 130 140 150
LRGQHLPAWI HFPDVERVEW ANKIISQTWP YLSMIMESKF REKLEPKIRE
160 170 180 190 200
KSIHLRTFTF TKLYFGQKCP RVNGVKAHTN TCNRRRVTVD LQICYIGDCE
210 220 230 240 250
ISVELQKIQA GVNGIQLQGT LRVILEPLLV DKPFVGAVTV FFLQKPHLQI
260 270 280 290 300
NWTGLTNLLD APGINDVSDS LLEDLIATHL VLPNRVTVPV KKGLDLTNLR
310 320 330 340 350
FPLPCGVIRV HLLEAEQLAQ KDNFLGLRGK SDPYAKVSIG LQHFRSRTIY
360 370 380 390 400
RNLNPTWNEV FEFMVYEVPG QDLEVDLYDE DTDRDDFLGS LQICLGDVMT
410 420 430 440 450
NRVVDEWFVL NDTTSGRLHL RLEWLSLLTD QEVLTEDHGG LSTAILVVFL
460 470 480 490 500
ESACNLPRNP FDYLNGEYRA KKLSRFARNK VSKDPSSYVK LSVGKKTHTS
510 520 530 540 550
KTCPHNKDPV WSQVFSFFVH NVATERLHLK VLDDDQECAL GMLEVPLCQI
560 570 580 590 600
LPYADLTLEQ RFQLDHSGLD SLISMRLVLR FLQVEERELG SPYTGPEALK
610 620 630 640 650
KGPLLIKKVA TNQGPKAQPQ EEGPTDLPCP PDPASDTKDV SRSTTTTTSA
660 670 680 690 700
TTVATEPTSQ ETGPEPKGKD SAKRFCEPIG EKKSPATIFL TVPGPHSPGP
710 720 730 740 750
IKSPRPMKCP ASPFAWPPKR LAPSMSSLNS LASSCFDLAD ISLNIEGGDL
760 770 780 790 800
RRRQLGEIQL TVRYVCLRRC LSVLINGCRN LTPCTSSGAD PYVRVYLLPE
810 820 830 840 850
RKWACRKKTS VKRKTLEPLF DETFEFFVPM EEVKKRSLDV AVKNSRPLGS
860 870 880
HRRKELGKVL IDLSKEDLIK GFSQWYELTP NGQPRS
Length:886
Mass (Da):100,035
Last modified:November 28, 2006 - v1
Checksum:i5CFE68F790D11B9B
GO
Isoform 2 (identifier: A0FGR9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     479-501: NKVSKDPSSYVKLSVGKKTHTSK → VKQGQQRPFFLCQTICRQEDTYK
     502-886: Missing.

Show »
Length:501
Mass (Da):57,502
Checksum:i4B0951E0B2D5DDF1
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_038117246P → Q1 PublicationCorresponds to variant dbSNP:rs17857138Ensembl.1
Natural variantiVAR_038118416G → R. Corresponds to variant dbSNP:rs6772467Ensembl.1
Natural variantiVAR_053835590G → R. Corresponds to variant dbSNP:rs10935282Ensembl.1
Natural variantiVAR_062173662T → S. Corresponds to variant dbSNP:rs35537868Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_030424479 – 501NKVSK…THTSK → VKQGQQRPFFLCQTICRQED TYK in isoform 2. 2 PublicationsAdd BLAST23
Alternative sequenceiVSP_030425502 – 886Missing in isoform 2. 2 PublicationsAdd BLAST385

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ993202 mRNA Translation: ABJ97707.1
AK289530 mRNA Translation: BAF82219.1
BC037292 mRNA Translation: AAH37292.1
AJ303366 mRNA Translation: CAC33888.1
CCDSiCCDS3101.2 [A0FGR9-1]
RefSeqiNP_001309760.1, NM_001322831.1 [A0FGR9-1]
NP_114119.2, NM_031913.4 [A0FGR9-1]
UniGeneiHs.477711

Genome annotation databases

EnsembliENST00000389567; ENSP00000374218; ENSG00000158220 [A0FGR9-1]
ENST00000490835; ENSP00000417388; ENSG00000158220 [A0FGR9-2]
GeneIDi83850
KEGGihsa:83850
UCSCiuc003esk.4 human [A0FGR9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiESYT3_HUMAN
AccessioniPrimary (citable) accession number: A0FGR9
Secondary accession number(s): A8K0G5
, Q6ZV21, Q8NDZ5, Q9BQR9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: November 28, 2006
Last modified: March 28, 2018
This is version 99 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, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health