ESYT3_HUMAN
ID ESYT3_HUMAN Reviewed; 886 AA.
AC A0FGR9; A8K0G5; Q6ZV21; Q8NDZ5; Q9BQR9;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Extended synaptotagmin-3 {ECO:0000305};
DE Short=E-Syt3 {ECO:0000303|PubMed:29469807};
DE AltName: Full=Chr3Syt;
GN Name=ESYT3 {ECO:0000312|HGNC:HGNC:24295}; Synonyms=FAM62C;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=17360437; DOI=10.1073/pnas.0611725104;
RA Min S.-W., Chang W.-P., Suedhof T.C.;
RT "E-Syts, a family of membranous Ca2+-sensor proteins with multiple C2
RT domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:3823-3828(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum, and Colon;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLN-246.
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 780-823 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11543631; DOI=10.1006/geno.2001.6619;
RA Craxton M.A.;
RT "Genomic analysis of synaptotagmin genes.";
RL Genomics 77:43-49(2001).
RN [5]
RP LIPID-BINDING, FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND INTERACTION
RP WITH ESYT1 AND ESYT2.
RX PubMed=23791178; DOI=10.1016/j.cell.2013.05.026;
RA Giordano F., Saheki Y., Idevall-Hagren O., Colombo S.F., Pirruccello M.,
RA Milosevic I., Gracheva E.O., Bagriantsev S.N., Borgese N., De Camilli P.;
RT "PI(4,5)P(2)-dependent and Ca(2+)-regulated ER-PM interactions mediated by
RT the extended synaptotagmins.";
RL Cell 153:1494-1509(2013).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=30220461; DOI=10.1016/j.cell.2018.08.033;
RA Sandhu J., Li S., Fairall L., Pfisterer S.G., Gurnett J.E., Xiao X.,
RA Weston T.A., Vashi D., Ferrari A., Orozco J.L., Hartman C.L.,
RA Strugatsky D., Lee S.D., He C., Hong C., Jiang H., Bentolila L.A.,
RA Gatta A.T., Levine T.P., Ferng A., Lee R., Ford D.A., Young S.G.,
RA Ikonen E., Schwabe J.W.R., Tontonoz P.;
RT "Aster proteins facilitate nonvesicular plasma membrane to ER cholesterol
RT transport in mammalian cells.";
RL Cell 175:514-529(2018).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=29469807; DOI=10.7554/elife.31019;
RA Besprozvannaya M., Dickson E., Li H., Ginburg K.S., Bers D.M., Auwerx J.,
RA Nunnari J.;
RT "GRAM domain proteins specialize functionally distinct ER-PM contact sites
RT in human cells.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Binds glycerophospholipids in a barrel-like domain and may
CC play a role in cellular lipid transport (By similarity). Tethers the
CC endoplasmic reticulum to the cell membrane and promotes the formation
CC of appositions between the endoplasmic reticulum and the cell membrane.
CC {ECO:0000250, ECO:0000269|PubMed:23791178}.
CC -!- SUBUNIT: Interacts with ESYT1 and ESYT2. {ECO:0000269|PubMed:23791178}.
CC -!- INTERACTION:
CC A0FGR9; Q9BSJ8: ESYT1; NbExp=4; IntAct=EBI-8771391, EBI-355956;
CC A0FGR9; A0FGR8: ESYT2; NbExp=4; IntAct=EBI-8771391, EBI-3184170;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17360437,
CC ECO:0000269|PubMed:29469807}; Peripheral membrane protein
CC {ECO:0000269|PubMed:17360437}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:29469807}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Localizes to endoplasmic reticulum-plasma membrane
CC contact sites (EPCS) (PubMed:29469807, PubMed:30220461). Recruited to
CC the cell membrane via the third C2 domain.
CC {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:29469807,
CC ECO:0000269|PubMed:30220461}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A0FGR9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A0FGR9-2; Sequence=VSP_030424, VSP_030425;
CC -!- TISSUE SPECIFICITY: Widely expressed with high level in cerebellum and
CC skin. {ECO:0000269|PubMed:17360437}.
CC -!- DOMAIN: Anchored to the endoplasmic reticulum membrane by a
CC transmembrane hairpin structure; both N-terminus and C-terminus are
CC cytoplasmic. {ECO:0000269|PubMed:23791178}.
CC -!- DOMAIN: The C2 domains mediate lipid and calcium binding. The N-
CC terminal C2 domain binds calcium ions and is important for calcium-
CC dependent lipid binding and interaction with membranes. Two calcium
CC ions are bound at a high-affinity site and a third calcium ion is bound
CC with lower affinity. May bind up to four calcium ions. In contrast, the
CC second C2 domain apparently does not bind calcium (By similarity). The
CC third C2 domain mediates interaction with membranes enriched in
CC phosphatidylinositol 4,5-bisphosphate and is required for location at
CC the cell membrane (PubMed:23791178). {ECO:0000250,
CC ECO:0000269|PubMed:23791178}.
CC -!- DOMAIN: The SMP-LTD domain is a barrel-like domain that binds
CC glycerophospholipids in its interior (By similarity).
CC {ECO:0000250|UniProtKB:A0FGR8}.
CC -!- SIMILARITY: Belongs to the extended synaptotagmin family.
CC {ECO:0000305}.
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DR EMBL; DQ993202; ABJ97707.1; -; mRNA.
DR EMBL; AK289530; BAF82219.1; -; mRNA.
DR EMBL; BC037292; AAH37292.1; -; mRNA.
DR EMBL; AJ303366; CAC33888.1; -; mRNA.
DR CCDS; CCDS3101.2; -. [A0FGR9-1]
DR RefSeq; NP_001309760.1; NM_001322831.1. [A0FGR9-1]
DR RefSeq; NP_114119.2; NM_031913.4. [A0FGR9-1]
DR AlphaFoldDB; A0FGR9; -.
DR SMR; A0FGR9; -.
DR BioGRID; 123766; 4.
DR CORUM; A0FGR9; -.
DR DIP; DIP-61998N; -.
DR IntAct; A0FGR9; 3.
DR STRING; 9606.ENSP00000374218; -.
DR TCDB; 9.A.57.1.3; the extended-synaptotagmin (e-syt) family.
DR iPTMnet; A0FGR9; -.
DR PhosphoSitePlus; A0FGR9; -.
DR BioMuta; ESYT3; -.
DR EPD; A0FGR9; -.
DR jPOST; A0FGR9; -.
DR MassIVE; A0FGR9; -.
DR PaxDb; A0FGR9; -.
DR PeptideAtlas; A0FGR9; -.
DR PRIDE; A0FGR9; -.
DR ProteomicsDB; 35; -. [A0FGR9-1]
DR Antibodypedia; 33435; 63 antibodies from 15 providers.
DR DNASU; 83850; -.
DR Ensembl; ENST00000389567.9; ENSP00000374218.4; ENSG00000158220.14. [A0FGR9-1]
DR Ensembl; ENST00000490835.5; ENSP00000417388.1; ENSG00000158220.14. [A0FGR9-2]
DR GeneID; 83850; -.
DR KEGG; hsa:83850; -.
DR MANE-Select; ENST00000389567.9; ENSP00000374218.4; NM_031913.5; NP_114119.2.
DR UCSC; uc003esk.4; human. [A0FGR9-1]
DR CTD; 83850; -.
DR DisGeNET; 83850; -.
DR GeneCards; ESYT3; -.
DR HGNC; HGNC:24295; ESYT3.
DR HPA; ENSG00000158220; Tissue enhanced (brain, skin).
DR neXtProt; NX_A0FGR9; -.
DR OpenTargets; ENSG00000158220; -.
DR PharmGKB; PA165697118; -.
DR VEuPathDB; HostDB:ENSG00000158220; -.
DR eggNOG; KOG1012; Eukaryota.
DR GeneTree; ENSGT00940000161072; -.
DR HOGENOM; CLU_012047_1_0_1; -.
DR InParanoid; A0FGR9; -.
DR OMA; AKGFCEP; -.
DR OrthoDB; 52746at2759; -.
DR PhylomeDB; A0FGR9; -.
DR TreeFam; TF324255; -.
DR PathwayCommons; A0FGR9; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR SignaLink; A0FGR9; -.
DR BioGRID-ORCS; 83850; 11 hits in 1069 CRISPR screens.
DR ChiTaRS; ESYT3; human.
DR GenomeRNAi; 83850; -.
DR Pharos; A0FGR9; Tbio.
DR PRO; PR:A0FGR9; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; A0FGR9; protein.
DR Bgee; ENSG00000158220; Expressed in right hemisphere of cerebellum and 103 other tissues.
DR ExpressionAtlas; A0FGR9; baseline and differential.
DR Genevisible; A0FGR9; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0140268; C:endoplasmic reticulum-plasma membrane contact site; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:FlyBase.
DR GO; GO:0031227; C:intrinsic component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0044232; C:organelle membrane contact site; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IBA:GO_Central.
DR GO; GO:0031210; F:phosphatidylcholine binding; IBA:GO_Central.
DR GO; GO:0008429; F:phosphatidylethanolamine binding; IBA:GO_Central.
DR GO; GO:0035091; F:phosphatidylinositol binding; IBA:GO_Central.
DR GO; GO:0061817; P:endoplasmic reticulum-plasma membrane tethering; IEA:InterPro.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR CDD; cd08391; C2A_C2C_Synaptotagmin_like; 1.
DR CDD; cd04050; C2B_Synaptotagmin-like; 1.
DR CDD; cd04030; C2C_KIAA1228; 1.
DR Gene3D; 2.60.40.150; -; 3.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037752; C2C_KIAA1228.
DR InterPro; IPR037733; Ext_Synaptotagmin_C2A.
DR InterPro; IPR037749; Ext_Synaptotagmin_C2B.
DR InterPro; IPR031468; SMP_LBD.
DR InterPro; IPR039010; Synaptotagmin_SMP.
DR Pfam; PF00168; C2; 3.
DR Pfam; PF17047; SMP_LBD; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR SMART; SM00239; C2; 3.
DR SUPFAM; SSF49562; SSF49562; 3.
DR PROSITE; PS50004; C2; 3.
DR PROSITE; PS51847; SMP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell membrane; Endoplasmic reticulum;
KW Lipid transport; Lipid-binding; Membrane; Metal-binding;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..886
FT /note="Extended synaptotagmin-3"
FT /id="PRO_0000314899"
FT TOPO_DOM 1..29
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 30..50
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 51..71
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 72..886
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 114..291
FT /note="SMP-LTD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01194"
FT DOMAIN 291..408
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 426..566
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 754..876
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 613..673
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 801..808
FT /note="Required for phosphatidylinositol 4,5-bisphosphate-
FT dependent location at the cell membrane"
FT /evidence="ECO:0000250"
FT COMPBIAS 637..665
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 321
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 322
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 322
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 332
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 379
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 379
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 380
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 381
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 381
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 381
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 383
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 385
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 386
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT VAR_SEQ 479..501
FT /note="NKVSKDPSSYVKLSVGKKTHTSK -> VKQGQQRPFFLCQTICRQEDTYK
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_030424"
FT VAR_SEQ 502..886
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_030425"
FT VARIANT 246
FT /note="P -> Q (in dbSNP:rs17857138)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_038117"
FT VARIANT 416
FT /note="G -> R (in dbSNP:rs6772467)"
FT /id="VAR_038118"
FT VARIANT 590
FT /note="G -> R (in dbSNP:rs10935282)"
FT /id="VAR_053835"
FT VARIANT 662
FT /note="T -> S (in dbSNP:rs35537868)"
FT /id="VAR_062173"
SQ SEQUENCE 886 AA; 100035 MW; 5CFE68F790D11B9B CRC64;
MRAEEPCAPG APSALGAQRT PGPELRLSSQ LLPELCTFVV RVLFYLGPVY LAGYLGLSIT
WLLLGALLWM WWRRNRRGKL GRLAAAFEFL DNEREFISRE LRGQHLPAWI HFPDVERVEW
ANKIISQTWP YLSMIMESKF REKLEPKIRE KSIHLRTFTF TKLYFGQKCP RVNGVKAHTN
TCNRRRVTVD LQICYIGDCE ISVELQKIQA GVNGIQLQGT LRVILEPLLV DKPFVGAVTV
FFLQKPHLQI NWTGLTNLLD APGINDVSDS LLEDLIATHL VLPNRVTVPV KKGLDLTNLR
FPLPCGVIRV HLLEAEQLAQ KDNFLGLRGK SDPYAKVSIG LQHFRSRTIY RNLNPTWNEV
FEFMVYEVPG QDLEVDLYDE DTDRDDFLGS LQICLGDVMT NRVVDEWFVL NDTTSGRLHL
RLEWLSLLTD QEVLTEDHGG LSTAILVVFL ESACNLPRNP FDYLNGEYRA KKLSRFARNK
VSKDPSSYVK LSVGKKTHTS KTCPHNKDPV WSQVFSFFVH NVATERLHLK VLDDDQECAL
GMLEVPLCQI LPYADLTLEQ RFQLDHSGLD SLISMRLVLR FLQVEERELG SPYTGPEALK
KGPLLIKKVA TNQGPKAQPQ EEGPTDLPCP PDPASDTKDV SRSTTTTTSA TTVATEPTSQ
ETGPEPKGKD SAKRFCEPIG EKKSPATIFL TVPGPHSPGP IKSPRPMKCP ASPFAWPPKR
LAPSMSSLNS LASSCFDLAD ISLNIEGGDL RRRQLGEIQL TVRYVCLRRC LSVLINGCRN
LTPCTSSGAD PYVRVYLLPE RKWACRKKTS VKRKTLEPLF DETFEFFVPM EEVKKRSLDV
AVKNSRPLGS HRRKELGKVL IDLSKEDLIK GFSQWYELTP NGQPRS
