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Protein

Extended synaptotagmin-2

Gene

ESYT2

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

Functioni

Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Plays a role in FGF signaling via its role in the rapid internalization of FGFR1 that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi400Calcium 1; via carbonyl oxygen1 Publication1
Metal bindingi401Calcium 11 Publication1
Metal bindingi401Calcium 21 Publication1
Metal bindingi413Calcium 21 Publication1
Metal bindingi460Calcium 11 Publication1
Metal bindingi460Calcium 21 Publication1
Metal bindingi461Calcium 2; via carbonyl oxygen1 Publication1
Metal bindingi462Calcium 11 Publication1
Metal bindingi462Calcium 21 Publication1
Metal bindingi462Calcium 3; via carbonyl oxygen1 Publication1
Metal bindingi464Calcium 3; via carbonyl oxygen1 Publication1
Metal bindingi466Calcium 31 Publication1
Metal bindingi467Calcium 11 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-1660662 Glycosphingolipid metabolism

Protein family/group databases

TCDBi9.A.57.1.2 the extended-synaptotagmin (e-syt) family

Names & Taxonomyi

Protein namesi
Recommended name:
Extended synaptotagmin-2Curated
Short name:
E-Syt21 Publication
Alternative name(s):
Chr2Syt
Gene namesi
Name:ESYT2Imported
Synonyms:FAM62B, KIAA1228
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000117868.15
HGNCiHGNC:22211 ESYT2
neXtProtiNX_A0FGR8

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 – 103CytoplasmicSequence analysisAdd BLAST103
Transmembranei104 – 124HelicalSequence analysisAdd BLAST21
Topological domaini125 – 127LumenalSequence analysis3
Transmembranei128 – 148HelicalSequence analysisAdd BLAST21
Topological domaini149 – 921CytoplasmicSequence analysisAdd BLAST773

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi401D → A: Abolishes calcium binding; when associated with A-413. 1 Publication1
Mutagenesisi413D → A: Abolishes calcium binding; when associated with A-401. 1 Publication1
Mutagenesisi413D → N: Strongly reduces calcium binding. 1 Publication1
Mutagenesisi466D → A: Impairs binding of the third calcium ion, but has no effect on the binding of the other two calcium ions. 1 Publication1
Mutagenesisi833 – 840KRRSGRRK → AAASGAAA: Abolishes location at the cell membrane. 1 Publication8

Organism-specific databases

OpenTargetsiENSG00000117868
PharmGKBiPA165617947

Polymorphism and mutation databases

BioMutaiESYT2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002782581 – 921Extended synaptotagmin-2Add BLAST921

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei691PhosphoserineCombined sources1
Modified residuei693PhosphoserineCombined sources1
Modified residuei705PhosphothreonineCombined sources1
Modified residuei736PhosphoserineCombined sources1
Modified residuei738PhosphoserineBy similarity1
Modified residuei739PhosphoserineCombined sources1
Modified residuei743PhosphoserineCombined sources1
Modified residuei748PhosphoserineCombined sources1
Modified residuei755PhosphoserineCombined sources1
Modified residuei758PhosphoserineCombined sources1
Modified residuei761PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiA0FGR8
MaxQBiA0FGR8
PaxDbiA0FGR8
PRIDEiA0FGR8
ProteomicsDBi30
31 [A0FGR8-2]
32 [A0FGR8-4]
33 [A0FGR8-5]
34 [A0FGR8-6]

PTM databases

iPTMnetiA0FGR8
PhosphoSitePlusiA0FGR8
SwissPalmiA0FGR8

Expressioni

Tissue specificityi

Widely expressed with high level in cerebellum.1 Publication

Gene expression databases

BgeeiENSG00000117868 Expressed in 209 organ(s), highest expression level in placenta
CleanExiHS_FAM62B
ExpressionAtlasiA0FGR8 baseline and differential
GenevisibleiA0FGR8 HS

Organism-specific databases

HPAiHPA002132

Interactioni

Subunit structurei

Homodimer. Interacts with ESYT1 and ESYT3. Interacts with FGFR1 that has been activated by FGF1 binding. Interacts with the AP-2 complex; identified in a complex with the AP-2 complex and FGFR1.4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121556, 39 interactors
DIPiDIP-61039N
IntActiA0FGR8, 32 interactors
MINTiA0FGR8
STRINGi9606.ENSP00000251527

Structurei

Secondary structure

1921
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliA0FGR8
SMRiA0FGR8
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiA0FGR8

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini191 – 370SMP-LTDPROSITE-ProRule annotation1 PublicationAdd BLAST180
Domaini372 – 473C2 1PROSITE-ProRule annotationAdd BLAST102
Domaini523 – 617C2 2PROSITE-ProRule annotationAdd BLAST95
Domaini788 – 892C2 3PROSITE-ProRule annotationAdd BLAST105

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni833 – 840Required for phosphatidylinositol 4,5-bisphosphate-dependent location at the cell membrane8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi736 – 739Poly-Ser4

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 (PubMed:24373768). 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).2 Publications
The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior; can bind two lipid molecules simultaneously. Binds a variety of lipids, including phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol (PubMed:24847877).1 Publication

Sequence similaritiesi

Belongs to the extended synaptotagmin family.Curated

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410ISCC Eukaryota
ENOG410XPR4 LUCA
GeneTreeiENSGT00550000074417
HOVERGENiHBG055795
InParanoidiA0FGR8
PhylomeDBiA0FGR8
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
IPR039010 Synaptotagmin_SMP
PfamiView protein in Pfam
PF00168 C2, 3 hits
PF17047 SMP_LBD, 1 hit
SMARTiView protein in SMART
SM00239 C2, 3 hits
PROSITEiView protein in PROSITE
PS50004 C2, 3 hits
PS51847 SMP, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: A0FGR8-1) [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
MTANRDAALS SHRHPGCAQR PRTPTFASSS QRRSAFGFDD GNFPGLGERS
60 70 80 90 100
HAPGSRLGAR RRAKTARGLR GHRQRGAGAG LSRPGSARAP SPPRPGGPEN
110 120 130 140 150
PGGVLSVELP GLLAQLARSF ALLLPVYALG YLGLSFSWVL LALALLAWCR
160 170 180 190 200
RSRGLKALRL CRALALLEDE ERVVRLGVRA CDLPAWVHFP DTERAEWLNK
210 220 230 240 250
TVKHMWPFIC QFIEKLFRET IEPAVRGANT HLSTFSFTKV DVGQQPLRIN
260 270 280 290 300
GVKVYTENVD KRQIILDLQI SFVGNCEIDL EIKRYFCRAG VKSIQIHGTM
310 320 330 340 350
RVILEPLIGD MPLVGALSIF FLRKPLLEIN WTGLTNLLDV PGLNGLSDTI
360 370 380 390 400
ILDIISNYLV LPNRITVPLV SEVQIAQLRF PVPKGVLRIH FIEAQDLQGK
410 420 430 440 450
DTYLKGLVKG KSDPYGIIRV GNQIFQSRVI KENLSPKWNE VYEALVYEHP
460 470 480 490 500
GQELEIELFD EDPDKDDFLG SLMIDLIEVE KERLLDEWFT LDEVPKGKLH
510 520 530 540 550
LRLEWLTLMP NASNLDKVLT DIKADKDQAN DGLSSALLIL YLDSARNLPS
560 570 580 590 600
GKKISSNPNP VVQMSVGHKA QESKIRYKTN EPVWEENFTF FIHNPKRQDL
610 620 630 640 650
EVEVRDEQHQ CSLGNLKVPL SQLLTSEDMT VSQRFQLSNS GPNSTIKMKI
660 670 680 690 700
ALRVLHLEKR ERPPDHQHSA QVKRPSVSKE GRKTSIKSHM SGSPGPGGSN
710 720 730 740 750
TAPSTPVIGG SDKPGMEEKA QPPEAGPQGL HDLGRSSSSL LASPGHISVK
760 770 780 790 800
EPTPSIASDI SLPIATQELR QRLRQLENGT TLGQSPLGQI QLTIRHSSQR
810 820 830 840 850
NKLIVVVHAC RNLIAFSEDG SDPYVRMYLL PDKRRSGRRK THVSKKTLNP
860 870 880 890 900
VFDQSFDFSV SLPEVQRRTL DVAVKNSGGF LSKDKGLLGK VLVALASEEL
910 920
AKGWTQWYDL TEDGTRPQAM T
Length:921
Mass (Da):102,357
Last modified:November 28, 2006 - v1
Checksum:iD57F1BD9BB0A0C8A
GO
Isoform 2 (identifier: A0FGR8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-97: MTANRDAALS...RAPSPPRPGG → MTPPSRAEAG...GAGGAGGRAA

Note: No experimental confirmation available.
Show »
Length:893
Mass (Da):98,902
Checksum:i9C059B137A2F1EFB
GO
Isoform 4 (identifier: A0FGR8-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-204: Missing.
     706-731: PVIGGSDKPGMEEKAQPPEAGPQGLH → SQSRSRPPASPRTSRCPSPPRSCGKG
     732-921: Missing.

Note: No experimental confirmation available.
Show »
Length:527
Mass (Da):59,403
Checksum:iE4257349511C9C28
GO
Isoform 5 (identifier: A0FGR8-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-593: Missing.
     594-603: NPKRQDLEVE → MPVLPPCVLQ

Note: No experimental confirmation available.
Show »
Length:328
Mass (Da):35,846
Checksum:iEF531CFF2A35D17C
GO
Isoform 6 (identifier: A0FGR8-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     550-550: S → SNPLEFNPDVLKKTAVQRALKS

Note: No experimental confirmation available.
Show »
Length:942
Mass (Da):104,708
Checksum:i207D6C010DB58248
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7BXI1H7BXI1_HUMAN
Extended synaptotagmin-2
ESYT2
884Annotation score:
A0A087WXU3A0A087WXU3_HUMAN
Extended synaptotagmin-2
ESYT2
921Annotation score:

Sequence cautioni

The sequence BAA91539 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC85769 differs from that shown. Reason: Frameshift at position 800.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti141L → V in CAH10642 (PubMed:17974005).Curated1
Sequence conflicti612S → P in BAC85769 (PubMed:14702039).Curated1
Sequence conflicti615N → S in BAC86489 (PubMed:14702039).Curated1
Sequence conflicti795R → Q in BAC85769 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030725210C → S. Corresponds to variant dbSNP:rs13233513Ensembl.1
Natural variantiVAR_030726638S → G1 PublicationCorresponds to variant dbSNP:rs2305473Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0232361 – 593Missing in isoform 5. 1 PublicationAdd BLAST593
Alternative sequenceiVSP_0232381 – 204Missing in isoform 4. 1 PublicationAdd BLAST204
Alternative sequenceiVSP_0232391 – 97MTANR…PRPGG → MTPPSRAEAGVRRSRVPSEG RWRGAEPPGISASTQPASAG RAARHCGAMSGARGEGPEAG AGGAGGRAA in isoform 2. 1 PublicationAdd BLAST97
Alternative sequenceiVSP_038324550S → SNPLEFNPDVLKKTAVQRAL KS in isoform 6. 1 Publication1
Alternative sequenceiVSP_023240594 – 603NPKRQDLEVE → MPVLPPCVLQ in isoform 5. 1 Publication10
Alternative sequenceiVSP_023241706 – 731PVIGG…PQGLH → SQSRSRPPASPRTSRCPSPP RSCGKG in isoform 4. 1 PublicationAdd BLAST26
Alternative sequenceiVSP_023242732 – 921Missing in isoform 4. 1 PublicationAdd BLAST190

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ993201 mRNA Translation: ABJ97706.1
AY368150 mRNA Translation: AAR89381.1
AK001181 mRNA Translation: BAA91539.1 Different initiation.
AK124091 mRNA Translation: BAC85769.1 Frameshift.
AK126214 mRNA Translation: BAC86489.1
CH236954 Genomic DNA Translation: EAL23931.1
AB033054 mRNA Translation: BAA86542.2
AL833233 mRNA Translation: CAH10642.1
BC013957 mRNA Translation: AAH13957.2
AJ303365 mRNA Translation: CAC33887.1
CCDSiCCDS34791.1 [A0FGR8-2]
RefSeqiNP_065779.1, NM_020728.2 [A0FGR8-2]
UniGeneiHs.490795

Genome annotation databases

EnsembliENST00000251527; ENSP00000251527; ENSG00000117868 [A0FGR8-2]
GeneIDi57488
KEGGihsa:57488
UCSCiuc003wob.2 human [A0FGR8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ993201 mRNA Translation: ABJ97706.1
AY368150 mRNA Translation: AAR89381.1
AK001181 mRNA Translation: BAA91539.1 Different initiation.
AK124091 mRNA Translation: BAC85769.1 Frameshift.
AK126214 mRNA Translation: BAC86489.1
CH236954 Genomic DNA Translation: EAL23931.1
AB033054 mRNA Translation: BAA86542.2
AL833233 mRNA Translation: CAH10642.1
BC013957 mRNA Translation: AAH13957.2
AJ303365 mRNA Translation: CAC33887.1
CCDSiCCDS34791.1 [A0FGR8-2]
RefSeqiNP_065779.1, NM_020728.2 [A0FGR8-2]
UniGeneiHs.490795

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DMGNMR-A785-913[»]
4NPJX-ray2.10A/B363-660[»]
4NPKX-ray2.55A363-660[»]
4P42X-ray2.44A/B191-662[»]
ProteinModelPortaliA0FGR8
SMRiA0FGR8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121556, 39 interactors
DIPiDIP-61039N
IntActiA0FGR8, 32 interactors
MINTiA0FGR8
STRINGi9606.ENSP00000251527

Protein family/group databases

TCDBi9.A.57.1.2 the extended-synaptotagmin (e-syt) family

PTM databases

iPTMnetiA0FGR8
PhosphoSitePlusiA0FGR8
SwissPalmiA0FGR8

Polymorphism and mutation databases

BioMutaiESYT2

Proteomic databases

EPDiA0FGR8
MaxQBiA0FGR8
PaxDbiA0FGR8
PRIDEiA0FGR8
ProteomicsDBi30
31 [A0FGR8-2]
32 [A0FGR8-4]
33 [A0FGR8-5]
34 [A0FGR8-6]

Protocols and materials databases

DNASUi57488
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000251527; ENSP00000251527; ENSG00000117868 [A0FGR8-2]
GeneIDi57488
KEGGihsa:57488
UCSCiuc003wob.2 human [A0FGR8-1]

Organism-specific databases

CTDi57488
EuPathDBiHostDB:ENSG00000117868.15
GeneCardsiESYT2
H-InvDBiHIX0007266
HGNCiHGNC:22211 ESYT2
HPAiHPA002132
neXtProtiNX_A0FGR8
OpenTargetsiENSG00000117868
PharmGKBiPA165617947
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ISCC Eukaryota
ENOG410XPR4 LUCA
GeneTreeiENSGT00550000074417
HOVERGENiHBG055795
InParanoidiA0FGR8
PhylomeDBiA0FGR8
TreeFamiTF324255

Enzyme and pathway databases

ReactomeiR-HSA-1660662 Glycosphingolipid metabolism

Miscellaneous databases

ChiTaRSiESYT2 human
EvolutionaryTraceiA0FGR8
GeneWikiiFAM62B
GenomeRNAii57488
PROiPR:A0FGR8

Gene expression databases

BgeeiENSG00000117868 Expressed in 209 organ(s), highest expression level in placenta
CleanExiHS_FAM62B
ExpressionAtlasiA0FGR8 baseline and differential
GenevisibleiA0FGR8 HS

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
IPR039010 Synaptotagmin_SMP
PfamiView protein in Pfam
PF00168 C2, 3 hits
PF17047 SMP_LBD, 1 hit
SMARTiView protein in SMART
SM00239 C2, 3 hits
PROSITEiView protein in PROSITE
PS50004 C2, 3 hits
PS51847 SMP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiESYT2_HUMAN
AccessioniPrimary (citable) accession number: A0FGR8
Secondary accession number(s): A4D229
, Q69YJ2, Q6UKI4, Q6ZTU0, Q6ZVU1, Q9BQS0, Q9NW47, Q9ULJ2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 20, 2007
Last sequence update: November 28, 2006
Last modified: November 7, 2018
This is version 121 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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