ESYT1_HUMAN
ID ESYT1_HUMAN Reviewed; 1104 AA.
AC Q9BSJ8; A0FGR7; A8K2S2; O94848; Q6PJN4; Q9H6J1; Q9H6W2; Q9Y416;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Extended synaptotagmin-1 {ECO:0000305};
DE Short=E-Syt1 {ECO:0000303|PubMed:29469807};
DE AltName: Full=Membrane-bound C2 domain-containing protein;
GN Name=ESYT1 {ECO:0000312|HGNC:HGNC:29534}; Synonyms=FAM62A, KIAA0747, MBC2;
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 1).
RC TISSUE=Hepatoma, Kidney, and Tongue;
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 GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 43-1104 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [6]
RP PROTEIN SEQUENCE OF 308-323; 446-457 AND 551-586, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma, and Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (NOV-2005) to UniProtKB.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 379-1104 (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-963 AND SER-1034, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-817, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-820 AND SER-963, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP SUBCELLULAR LOCATION.
RX PubMed=22250200; DOI=10.1242/jcs.085118;
RA Toulmay A., Prinz W.A.;
RT "A conserved membrane-binding domain targets proteins to organelle contact
RT sites.";
RL J. Cell Sci. 125:49-58(2012).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, LIPID-BINDING, MUTAGENESIS OF
RP ASP-663; ASP-675 AND 722-ASP--ASP-729, AND INTERACTION WITH ESYT2 AND
RP ESYT3.
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 [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-406 AND ASP-724.
RX PubMed=24183667; DOI=10.1016/j.celrep.2013.09.038;
RA Chang C.L., Hsieh T.S., Yang T.T., Rothberg K.G., Azizoglu D.B., Volk E.,
RA Liao J.C., Liou J.;
RT "Feedback regulation of receptor-induced Ca2+ signaling mediated by E-Syt1
RT and Nir2 at endoplasmic reticulum-plasma membrane junctions.";
RL Cell Rep. 5:813-825(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-820; SER-963 AND SER-1034,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-820; SER-941; THR-948;
RP SER-949 AND SER-963, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [21]
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). Binds calcium
CC (via the C2 domains) and translocates to sites of contact between the
CC endoplasmic reticulum and the cell membrane in response to increased
CC cytosolic calcium levels. Helps tether the endoplasmic reticulum to the
CC cell membrane and promotes the formation of appositions between the
CC endoplasmic reticulum and the cell membrane. {ECO:0000250,
CC ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24183667}.
CC -!- SUBUNIT: Interacts (phosphorylated form) with SLC2A4 (By similarity).
CC Interacts with ESYT2 and ESYT3. {ECO:0000250,
CC ECO:0000269|PubMed:23791178}.
CC -!- INTERACTION:
CC Q9BSJ8; Q9BSJ8: ESYT1; NbExp=2; IntAct=EBI-355956, EBI-355956;
CC Q9BSJ8; A0FGR8: ESYT2; NbExp=6; IntAct=EBI-355956, EBI-3184170;
CC Q9BSJ8; A0FGR9: ESYT3; NbExp=4; IntAct=EBI-355956, EBI-8771391;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:29469807}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:29469807}; Peripheral
CC membrane protein {ECO:0000269|PubMed:29469807}. Note=Localizes
CC primarily to the endoplasmic reticulum (PubMed:29469807). Recruited to
CC sites of contact between the endoplasmic reticulum and the cell
CC membrane in response to increased cytosolic calcium levels
CC (PubMed:29469807, PubMed:22250200). {ECO:0000269|PubMed:22250200,
CC ECO:0000269|PubMed:29469807}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BSJ8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BSJ8-2; Sequence=VSP_018277;
CC -!- TISSUE SPECIFICITY: Widely expressed. {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 translocation
CC to the cell membrane in response to increased cytosolic calcium levels
CC (PubMed:24183667 and PubMed:23791178). {ECO:0000250}.
CC -!- DOMAIN: The SMP-LTD domain is a barrel-like domain that can bind
CC various types of glycerophospholipids in its interior (By similarity).
CC {ECO:0000250|UniProtKB:A0FGR8}.
CC -!- PTM: Phosphorylated on Ser residues in insulin-treated adipocytes (in
CC vitro); this promotes interaction with SLC2A4. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the extended synaptotagmin family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15139.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB15268.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; DQ993200; ABJ97705.1; -; mRNA.
DR EMBL; AK025463; BAB15139.1; ALT_INIT; mRNA.
DR EMBL; AK025878; BAB15268.1; ALT_INIT; mRNA.
DR EMBL; AK290337; BAF83026.1; -; mRNA.
DR EMBL; CH471054; EAW96891.1; -; Genomic_DNA.
DR EMBL; BC004998; AAH04998.1; -; mRNA.
DR EMBL; AB018290; BAA34467.1; -; mRNA.
DR EMBL; AL050134; CAB43284.1; -; mRNA.
DR CCDS; CCDS53801.1; -. [Q9BSJ8-2]
DR CCDS; CCDS8904.1; -. [Q9BSJ8-1]
DR PIR; T08769; T08769.
DR PIR; T13156; T13156.
DR RefSeq; NP_001171725.1; NM_001184796.1. [Q9BSJ8-2]
DR RefSeq; NP_056107.1; NM_015292.2. [Q9BSJ8-1]
DR AlphaFoldDB; Q9BSJ8; -.
DR SMR; Q9BSJ8; -.
DR BioGRID; 116927; 234.
DR CORUM; Q9BSJ8; -.
DR DIP; DIP-57197N; -.
DR ELM; Q9BSJ8; -.
DR IntAct; Q9BSJ8; 61.
DR MINT; Q9BSJ8; -.
DR STRING; 9606.ENSP00000267113; -.
DR ChEMBL; CHEMBL3621033; -.
DR TCDB; 9.A.57.1.1; the extended-synaptotagmin (e-syt) family.
DR GlyGen; Q9BSJ8; 1 site, 2 O-linked glycans (1 site).
DR iPTMnet; Q9BSJ8; -.
DR PhosphoSitePlus; Q9BSJ8; -.
DR SwissPalm; Q9BSJ8; -.
DR BioMuta; ESYT1; -.
DR DMDM; 74733019; -.
DR OGP; Q9Y416; -.
DR CPTAC; CPTAC-198; -.
DR CPTAC; CPTAC-199; -.
DR EPD; Q9BSJ8; -.
DR jPOST; Q9BSJ8; -.
DR MassIVE; Q9BSJ8; -.
DR MaxQB; Q9BSJ8; -.
DR PaxDb; Q9BSJ8; -.
DR PeptideAtlas; Q9BSJ8; -.
DR PRIDE; Q9BSJ8; -.
DR ProteomicsDB; 78906; -. [Q9BSJ8-1]
DR ProteomicsDB; 78907; -. [Q9BSJ8-2]
DR Antibodypedia; 3015; 249 antibodies from 33 providers.
DR DNASU; 23344; -.
DR Ensembl; ENST00000267113.4; ENSP00000267113.4; ENSG00000139641.13. [Q9BSJ8-2]
DR Ensembl; ENST00000394048.10; ENSP00000377612.5; ENSG00000139641.13. [Q9BSJ8-1]
DR GeneID; 23344; -.
DR KEGG; hsa:23344; -.
DR MANE-Select; ENST00000394048.10; ENSP00000377612.5; NM_015292.3; NP_056107.1.
DR UCSC; uc001sjq.4; human. [Q9BSJ8-1]
DR CTD; 23344; -.
DR DisGeNET; 23344; -.
DR GeneCards; ESYT1; -.
DR HGNC; HGNC:29534; ESYT1.
DR HPA; ENSG00000139641; Low tissue specificity.
DR neXtProt; NX_Q9BSJ8; -.
DR OpenTargets; ENSG00000139641; -.
DR PharmGKB; PA165512688; -.
DR VEuPathDB; HostDB:ENSG00000139641; -.
DR eggNOG; KOG1012; Eukaryota.
DR GeneTree; ENSGT00940000156561; -.
DR HOGENOM; CLU_012047_0_0_1; -.
DR InParanoid; Q9BSJ8; -.
DR OMA; HPGQSKE; -.
DR PhylomeDB; Q9BSJ8; -.
DR TreeFam; TF324255; -.
DR PathwayCommons; Q9BSJ8; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-9035034; RHOF GTPase cycle.
DR SignaLink; Q9BSJ8; -.
DR BioGRID-ORCS; 23344; 6 hits in 1071 CRISPR screens.
DR ChiTaRS; ESYT1; human.
DR GeneWiki; FAM62A; -.
DR GenomeRNAi; 23344; -.
DR Pharos; Q9BSJ8; Tbio.
DR PRO; PR:Q9BSJ8; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9BSJ8; protein.
DR Bgee; ENSG00000139641; Expressed in adipose tissue of abdominal region and 205 other tissues.
DR ExpressionAtlas; Q9BSJ8; baseline and differential.
DR Genevisible; Q9BSJ8; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0031227; C:intrinsic component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA: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:0042802; F:identical protein binding; IPI:IntAct.
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:0120014; F:phospholipid transfer activity; IDA:UniProtKB.
DR GO; GO:0061817; P:endoplasmic reticulum-plasma membrane tethering; IEA:InterPro.
DR GO; GO:0120009; P:intermembrane lipid transfer; IDA:UniProtKB.
DR CDD; cd08391; C2A_C2C_Synaptotagmin_like; 2.
DR CDD; cd04050; C2B_Synaptotagmin-like; 2.
DR CDD; cd04030; C2C_KIAA1228; 1.
DR Gene3D; 2.60.40.150; -; 5.
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; 5.
DR Pfam; PF17047; SMP_LBD; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR SMART; SM00239; C2; 5.
DR SUPFAM; SSF49562; SSF49562; 5.
DR PROSITE; PS50004; C2; 5.
DR PROSITE; PS51847; SMP; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Calcium; Cell membrane; Coiled coil;
KW Direct protein sequencing; Endoplasmic reticulum; Lipid transport;
KW Lipid-binding; Membrane; Metal-binding; Phosphoprotein; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1104
FT /note="Extended synaptotagmin-1"
FT /id="PRO_0000234344"
FT TOPO_DOM 1..38
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 39..59
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 60..62
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 84..1104
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 135..313
FT /note="SMP-LTD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01194"
FT DOMAIN 312..433
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 460..580
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 627..751
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 777..899
FT /note="C2 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 971..1093
FT /note="C2 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 617..641
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 924..950
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1018..1025
FT /note="Required for phosphatidylinositol 4,5-bisphosphate-
FT dependent location at the cell membrane"
FT /evidence="ECO:0000250"
FT COILED 91..116
FT /evidence="ECO:0000255"
FT COMPBIAS 10..30
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 924..938
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 344
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 345
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 345
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 357
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 404
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 404
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 406
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 406
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 406
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 408
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 410
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 411
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 324
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000250|UniProtKB:Q3U7R1"
FT MOD_RES 817
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 820
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 941
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 948
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 949
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 963
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1009
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1X1"
FT MOD_RES 1034
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 491
FT /note="P -> PMVTSELYPPQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9872452"
FT /id="VSP_018277"
FT VARIANT 764
FT /note="R -> C (in dbSNP:rs35075600)"
FT /id="VAR_038190"
FT MUTAGEN 406
FT /note="D->A: No effect on translocation to sites of contact
FT between the endoplasmic reticulum and the cell membrane."
FT /evidence="ECO:0000269|PubMed:24183667"
FT MUTAGEN 663
FT /note="D->A: Abolishes location at the cell membrane; when
FT associated with A-675 and 722-A--A-729."
FT /evidence="ECO:0000269|PubMed:23791178"
FT MUTAGEN 675
FT /note="D->A: Abolishes location at the cell membrane; when
FT associated with A-675 and 722-A--A-729."
FT /evidence="ECO:0000269|PubMed:23791178"
FT MUTAGEN 722..729
FT /note="DKDLDKDD->AKALAKAA: Abolishes location at the cell
FT membrane; when associated with A-663 and A-675."
FT /evidence="ECO:0000269|PubMed:23791178"
FT MUTAGEN 724
FT /note="D->A: Loss of translocation to sites of contact
FT between the endoplasmic reticulum and the cell membrane."
FT /evidence="ECO:0000269|PubMed:24183667"
FT CONFLICT 133
FT /note="F -> L (in Ref. 2; BAF83026)"
FT /evidence="ECO:0000305"
FT CONFLICT 489
FT /note="D -> N (in Ref. 2; BAB15139)"
FT /evidence="ECO:0000305"
FT CONFLICT 738
FT /note="L -> F (in Ref. 2; BAB15139)"
FT /evidence="ECO:0000305"
FT CONFLICT 785
FT /note="S -> R (in Ref. 2; BAF83026)"
FT /evidence="ECO:0000305"
FT CONFLICT 998
FT /note="L -> P (in Ref. 2; BAB15139)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1104 AA; 122856 MW; E72B20C458B96F19 CRC64;
MERSPGEGPS PSPMDQPSAP SDPTDQPPAA HAKPDPGSGG QPAGPGAAGE ALAVLTSFGR
RLLVLIPVYL AGAVGLSVGF VLFGLALYLG WRRVRDEKER SLRAARQLLD DEEQLTAKTL
YMSHRELPAW VSFPDVEKAE WLNKIVAQVW PFLGQYMEKL LAETVAPAVR GSNPHLQTFT
FTRVELGEKP LRIIGVKVHP GQRKEQILLD LNISYVGDVQ IDVEVKKYFC KAGVKGMQLH
GVLRVILEPL IGDLPFVGAV SMFFIRRPTL DINWTGMTNL LDIPGLSSLS DTMIMDSIAA
FLVLPNRLLV PLVPDLQDVA QLRSPLPRGI IRIHLLAARG LSSKDKYVKG LIEGKSDPYA
LVRLGTQTFC SRVIDEELNP QWGETYEVMV HEVPGQEIEV EVFDKDPDKD DFLGRMKLDV
GKVLQASVLD DWFPLQGGQG QVHLRLEWLS LLSDAEKLEQ VLQWNWGVSS RPDPPSAAIL
VVYLDRAQDL PLKKGNKEPN PMVQLSIQDV TQESKAVYST NCPVWEEAFR FFLQDPQSQE
LDVQVKDDSR ALTLGALTLP LARLLTAPEL ILDQWFQLSS SGPNSRLYMK LVMRILYLDS
SEICFPTVPG CPGAWDVDSE NPQRGSSVDA PPRPCHTTPD SQFGTEHVLR IHVLEAQDLI
AKDRFLGGLV KGKSDPYVKL KLAGRSFRSH VVREDLNPRW NEVFEVIVTS VPGQELEVEV
FDKDLDKDDF LGRCKVRLTT VLNSGFLDEW LTLEDVPSGR LHLRLERLTP RPTAAELEEV
LQVNSLIQTQ KSAELAAALL SIYMERAEDL PLRKGTKHLS PYATLTVGDS SHKTKTISQT
SAPVWDESAS FLIRKPHTES LELQVRGEGT GVLGSLSLPL SELLVADQLC LDRWFTLSSG
QGQVLLRAQL GILVSQHSGV EAHSHSYSHS SSSLSEEPEL SGGPPHITSS APELRQRLTH
VDSPLEAPAG PLGQVKLTLW YYSEERKLVS IVHGCRSLRQ NGRDPPDPYV SLLLLPDKNR
GTKRRTSQKK RTLSPEFNER FEWELPLDEA QRRKLDVSVK SNSSFMSRER ELLGKVQLDL
AETDLSQGVA RWYDLMDNKD KGSS
