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Protein

Extended synaptotagmin-3

Gene

ESYT3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi321 – 3211Calcium 1; via carbonyl oxygenBy similarity
Metal bindingi322 – 3221Calcium 1By similarity
Metal bindingi322 – 3221Calcium 2By similarity
Metal bindingi332 – 3321Calcium 2By similarity
Metal bindingi379 – 3791Calcium 1By similarity
Metal bindingi379 – 3791Calcium 2By similarity
Metal bindingi380 – 3801Calcium 2; via carbonyl oxygenBy similarity
Metal bindingi381 – 3811Calcium 1By similarity
Metal bindingi381 – 3811Calcium 2By similarity
Metal bindingi381 – 3811Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi383 – 3831Calcium 3; via carbonyl oxygenBy similarity
Metal bindingi385 – 3851Calcium 3By similarity
Metal bindingi386 – 3861Calcium 1By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Lipid transport, Transport

Keywords - Ligandi

Calcium, Lipid-binding, Metal-binding

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

HGNCiHGNC:24295. ESYT3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2929CytoplasmicSequence analysisAdd
BLAST
Transmembranei30 – 5021HelicalSequence analysisAdd
BLAST
Transmembranei51 – 7121HelicalSequence analysisAdd
BLAST
Topological domaini72 – 886815CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
  • integral component of plasma membrane Source: FlyBase
  • intrinsic component of endoplasmic reticulum membrane Source: UniProtKB
  • organelle membrane contact site Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA165697118.

Polymorphism and mutation databases

BioMutaiESYT3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 886886Extended synaptotagmin-3PRO_0000314899Add
BLAST

Proteomic databases

EPDiA0FGR9.
PaxDbiA0FGR9.
PeptideAtlasiA0FGR9.
PRIDEiA0FGR9.

PTM databases

iPTMnetiA0FGR9.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiA0FGR9.
CleanExiHS_FAM62C.
ExpressionAtlasiA0FGR9. baseline and differential.
GenevisibleiA0FGR9. HS.

Organism-specific databases

HPAiHPA039200.

Interactioni

Subunit structurei

Interacts with ESYT1 and ESYT2.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ESYT1Q9BSJ83EBI-8771391,EBI-355956
ESYT2A0FGR83EBI-8771391,EBI-3184170

Protein-protein interaction databases

BioGridi123766. 1 interaction.
IntActiA0FGR9. 2 interactions.
STRINGi9606.ENSP00000374218.

Structurei

3D structure databases

ProteinModelPortaliA0FGR9.
SMRiA0FGR9. Positions 114-585, 755-886.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini293 – 392100C2 1PROSITE-ProRule annotationAdd
BLAST
Domaini430 – 544115C2 2PROSITE-ProRule annotationAdd
BLAST
Domaini756 – 860105C2 3PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni118 – 291174Glycerophospholipid-binding barrel-like domainBy similarityAdd
BLAST
Regioni801 – 8088Required for phosphatidylinositol 4,5-bisphosphate-dependent location at the cell membraneBy similarity

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
Contains a barrel-like domain that can bind various types of glycerophospholipids in its interior.By similarity

Sequence similaritiesi

Belongs to the extended synaptotagmin family.Curated
Contains 3 C2 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1012. Eukaryota.
ENOG410YCXU. LUCA.
GeneTreeiENSGT00550000074417.
HOGENOMiHOG000043080.
HOVERGENiHBG055795.
InParanoidiA0FGR9.
OMAiAWPPKRL.
OrthoDBiEOG7RNJZK.
PhylomeDBiA0FGR9.
TreeFamiTF324255.

Family and domain databases

Gene3Di2.60.40.150. 3 hits.
InterProiIPR000008. C2_dom.
IPR031468. SMP_LBD.
[Graphical view]
PfamiPF00168. C2. 3 hits.
PF17047. SMP_LBD. 1 hit.
[Graphical view]
PRINTSiPR00360. C2DOMAIN.
SMARTiSM00239. C2. 3 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 3 hits.
PROSITEiPS50004. C2. 3 hits.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti246 – 2461P → Q.1 Publication
Corresponds to variant rs17857138 [ dbSNP | Ensembl ].
VAR_038117
Natural varianti416 – 4161G → R.
Corresponds to variant rs6772467 [ dbSNP | Ensembl ].
VAR_038118
Natural varianti590 – 5901G → R.
Corresponds to variant rs10935282 [ dbSNP | Ensembl ].
VAR_053835
Natural varianti662 – 6621T → S.
Corresponds to variant rs35537868 [ dbSNP | Ensembl ].
VAR_062173

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei479 – 50123NKVSK…THTSK → VKQGQQRPFFLCQTICRQED TYK in isoform 2. 2 PublicationsVSP_030424Add
BLAST
Alternative sequencei502 – 886385Missing in isoform 2. 2 PublicationsVSP_030425Add
BLAST

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.
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

Cross-referencesi

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.
NP_114119.2. NM_031913.4. [A0FGR9-1]
UniGeneiHs.477711.

3D structure databases

ProteinModelPortaliA0FGR9.
SMRiA0FGR9. Positions 114-585, 755-886.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123766. 1 interaction.
IntActiA0FGR9. 2 interactions.
STRINGi9606.ENSP00000374218.

Protein family/group databases

TCDBi9.A.57.1.3. the extended-synaptotagmin (e-syt) family.

PTM databases

iPTMnetiA0FGR9.

Polymorphism and mutation databases

BioMutaiESYT3.

Proteomic databases

EPDiA0FGR9.
PaxDbiA0FGR9.
PeptideAtlasiA0FGR9.
PRIDEiA0FGR9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi83850.
GeneCardsiESYT3.
HGNCiHGNC:24295. ESYT3.
HPAiHPA039200.
neXtProtiNX_A0FGR9.
PharmGKBiPA165697118.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1012. Eukaryota.
ENOG410YCXU. LUCA.
GeneTreeiENSGT00550000074417.
HOGENOMiHOG000043080.
HOVERGENiHBG055795.
InParanoidiA0FGR9.
OMAiAWPPKRL.
OrthoDBiEOG7RNJZK.
PhylomeDBiA0FGR9.
TreeFamiTF324255.

Miscellaneous databases

GenomeRNAii83850.
PROiA0FGR9.

Gene expression databases

BgeeiA0FGR9.
CleanExiHS_FAM62C.
ExpressionAtlasiA0FGR9. baseline and differential.
GenevisibleiA0FGR9. HS.

Family and domain databases

Gene3Di2.60.40.150. 3 hits.
InterProiIPR000008. C2_dom.
IPR031468. SMP_LBD.
[Graphical view]
PfamiPF00168. C2. 3 hits.
PF17047. SMP_LBD. 1 hit.
[Graphical view]
PRINTSiPR00360. C2DOMAIN.
SMARTiSM00239. C2. 3 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 3 hits.
PROSITEiPS50004. C2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "E-Syts, a family of membranous Ca2+-sensor proteins with multiple C2 domains."
    Min S.-W., Chang W.-P., Suedhof T.C.
    Proc. Natl. Acad. Sci. U.S.A. 104:3823-3828(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Cerebellum and Colon.
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLN-246.
    Tissue: Testis.
  4. "Genomic analysis of synaptotagmin genes."
    Craxton M.A.
    Genomics 77:43-49(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 780-823 (ISOFORM 1).
    Tissue: Brain.
  5. "PI(4,5)P(2)-dependent and Ca(2+)-regulated ER-PM interactions mediated by the extended synaptotagmins."
    Giordano F., Saheki Y., Idevall-Hagren O., Colombo S.F., Pirruccello M., Milosevic I., Gracheva E.O., Bagriantsev S.N., Borgese N., De Camilli P.
    Cell 153:1494-1509(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: LIPID-BINDING, FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, INTERACTION WITH ESYT1 AND ESYT2.

Entry informationi

Entry nameiESYT3_HUMAN
AccessioniPrimary (citable) accession number: A0FGR9
Secondary accession number(s): A8K0G5
, Q6ZV21, Q8NDZ5, Q9BQR9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: November 28, 2006
Last modified: July 6, 2016
This is version 88 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 3
    Human chromosome 3: 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.