ID   ESYT1_RAT               Reviewed;        1088 AA.
AC   Q9Z1X1; Q3T1L3;
DT   16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   24-JAN-2024, entry version 136.
DE   RecName: Full=Extended synaptotagmin-1;
DE            Short=E-Syt1;
DE   AltName: Full=Membrane-bound C2 domain-containing protein;
DE   AltName: Full=vp115;
GN   Name=Esyt1; Synonyms=Fam62a, Mbc2;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC   STRAIN=Sprague-Dawley;
RX   PubMed=10350628; DOI=10.1016/s0167-4838(99)00068-0;
RA   Morris N.J., Ross S.A., Neveu J.M., Lane W.S., Lienhard G.E.;
RT   "Cloning and preliminary characterization of a 121 kDa protein with
RT   multiple predicted C2 domains.";
RL   Biochim. Biophys. Acta 1431:525-530(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Prostate;
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   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-993, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
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 (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with ESYT2 and ESYT3. Interacts (phosphorylated
CC       form) with SLC2A4 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:Q9BSJ8}; Multi-pass membrane protein
CC       {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q9BSJ8}; Peripheral
CC       membrane protein {ECO:0000250|UniProtKB:Q9BSJ8}. Note=Localizes
CC       primarily to the endoplasmic reticulum. Recruited to sites of contact
CC       between the endoplasmic reticulum and the cell membrane in response to
CC       increased cytosolic calcium levels. {ECO:0000250|UniProtKB:Q9BSJ8}.
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed with a higher expression in
CC       spleen and white adipose tissue. {ECO:0000269|PubMed:10350628}.
CC   -!- DOMAIN: Anchored to the endoplasmic reticulum membrane by a
CC       transmembrane hairpin structure; both N-terminus and C-terminus are
CC       cytoplasmic. {ECO:0000250}.
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. The third C2 domain
CC       mediates interaction with membranes enriched in phosphatidylinositol
CC       4,5-bisphosphate and is required for translocation to the cell membrane
CC       in response to increased cytosolic calcium levels (By similarity).
CC       {ECO:0000250}.
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   -!- 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}.
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DR   EMBL; AF099138; AAD10051.1; -; mRNA.
DR   EMBL; BC101857; AAI01858.1; -; mRNA.
DR   RefSeq; NP_058945.2; NM_017249.2.
DR   AlphaFoldDB; Q9Z1X1; -.
DR   SMR; Q9Z1X1; -.
DR   BioGRID; 248212; 2.
DR   IntAct; Q9Z1X1; 1.
DR   STRING; 10116.ENSRNOP00000070299; -.
DR   iPTMnet; Q9Z1X1; -.
DR   PhosphoSitePlus; Q9Z1X1; -.
DR   jPOST; Q9Z1X1; -.
DR   PaxDb; 10116-ENSRNOP00000006119; -.
DR   GeneID; 29579; -.
DR   KEGG; rno:29579; -.
DR   UCSC; RGD:3053; rat.
DR   AGR; RGD:3053; -.
DR   CTD; 23344; -.
DR   RGD; 3053; Esyt1.
DR   eggNOG; KOG1012; Eukaryota.
DR   InParanoid; Q9Z1X1; -.
DR   OrthoDB; 944695at2759; -.
DR   PhylomeDB; Q9Z1X1; -.
DR   TreeFam; TF324255; -.
DR   Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR   Reactome; R-RNO-9013404; RAC2 GTPase cycle.
DR   Reactome; R-RNO-9013405; RHOD GTPase cycle.
DR   Reactome; R-RNO-9013408; RHOG GTPase cycle.
DR   Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR   Reactome; R-RNO-9035034; RHOF GTPase cycle.
DR   Reactome; R-RNO-9840309; Glycosphingolipid biosynthesis.
DR   PRO; PR:Q9Z1X1; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
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; ISO:RGD.
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; ISS:UniProtKB.
DR   GO; GO:0061817; P:endoplasmic reticulum-plasma membrane tethering; IEA:InterPro.
DR   GO; GO:0120009; P:intermembrane lipid transfer; ISS: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; C2 domain; 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   PANTHER; PTHR45761:SF3; EXTENDED SYNAPTOTAGMIN-1; 1.
DR   PANTHER; PTHR45761; EXTENDED SYNAPTOTAGMIN-LIKE PROTEIN 2, ISOFORM C; 1.
DR   Pfam; PF00168; C2; 5.
DR   Pfam; PF17047; SMP_LBD; 1.
DR   PRINTS; PR00360; C2DOMAIN.
DR   SMART; SM00239; C2; 5.
DR   SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 5.
DR   PROSITE; PS50004; C2; 5.
DR   PROSITE; PS51847; SMP; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Calcium; Cell membrane; Endoplasmic reticulum;
KW   Lipid transport; Lipid-binding; Membrane; Metal-binding; Phosphoprotein;
KW   Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..1088
FT                   /note="Extended synaptotagmin-1"
FT                   /id="PRO_0000234347"
FT   TOPO_DOM        1..30
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        31..51
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        52..54
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        55..75
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        76..1088
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          127..305
FT                   /note="SMP-LTD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01194"
FT   DOMAIN          304..425
FT                   /note="C2 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   DOMAIN          446..572
FT                   /note="C2 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   DOMAIN          618..740
FT                   /note="C2 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   DOMAIN          771..888
FT                   /note="C2 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   DOMAIN          955..1077
FT                   /note="C2 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT   REGION          1..38
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          599..630
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          911..930
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1002..1009
FT                   /note="Required for phosphatidylinositol 4,5-bisphosphate-
FT                   dependent location at the cell membrane"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        606..630
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         336
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         337
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         337
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         349
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         396
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         396
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         398
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250"
FT   BINDING         398
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250"
FT   BINDING         398
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         400
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         402
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000250"
FT   BINDING         403
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:0000250|UniProtKB:Q9BSJ8"
FT   MOD_RES         316
FT                   /note="Phosphoserine; by CDK5"
FT                   /evidence="ECO:0000250|UniProtKB:Q3U7R1"
FT   MOD_RES         806
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BSJ8"
FT   MOD_RES         809
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BSJ8"
FT   MOD_RES         933
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BSJ8"
FT   MOD_RES         947
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9BSJ8"
FT   MOD_RES         993
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   CONFLICT        373
FT                   /note="H -> R (in Ref. 2; AAI01858)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1088 AA;  121159 MW;  E7E12D9737FFB89D CRC64;
     MERSPEEGAG PEPSGQSPAT DSTRERDGGS GVPPAGPGAA SEALAVLTSF GRRLLVLVPV
     YLAGAAGLSV GFVLFGLALY LGWRRVRDGK ERSLRAARQL LDDEERITAE TLYMSHRELP
     AWVSFPDVEK AEWLNKIVVQ VWPFLGQYME KLLAETVAPA VRGANPHLQT FTFTRVELGE
     KPVRIIGVKV HPSQRKDQIL LDLNVSYVGD LQIDVEVKKY FCKAGVKGMQ LHGVLRVILE
     PLIGDLPIVG AVSMFFIKRP TLDINWTGMT NLLDIPGLSS LSDTMIMDSI AAFLVLPNRL
     LVPLVPDLQD VAQLRSPLPR GIIRIHLLAA RGLSSKDKYV KGLIEGKSDP YALVRVGTQT
     FCSRVIDEEL NPHWGETYEV IVHEVPGQEI EVEVFDKDPD KDDFLGRMKL DVGKVLQAGV
     LDNWYPLQGG QGQVHLRLEW LSLLPDAEKL DQVLQWNRGI TSRPEPPSAA ILVVYLDRAQ
     DLPLKKGNKE PNPMVQLSVQ DVTQESKATY STNCPVWEEA FRFFLQDPRS QELDVQVKDD
     SRALTLGALT LPLARLLTAS ELTLDQWFQL SSSGPNSRLY MKLVMRILYL DSSEMRLPTE
     PGAQDWDSES PETGSSVDAP PRPYHTTPNS HFGTENVLRI HVLEAQDLIA KDRFLGGLVK
     GKSDPYVKLK VAGRSLRTHV VREDLNPRWN EVFEVIVTSI PGQELDIEVF DKDLDKDDFL
     GRYKVGLTTV LNSGFLDEWL TLEDVPSGRL HLRLERLSPR PTAAELEEVL QVNSLIQTQK
     SSELAAALLS VYLERSEDLP LRKGTKPPSP YAILTVGETS HKTKTVSQTS APIWEESASF
     LIRKPHAESL ELQVRGEGTG TLGSISLPLS ELLQEEQLCL DRWFALSGQG QVLMRVQLGI
     LVSQHSGVEA HSHSSSSLNE EPEVLGDPTH TASPVLEVRH RLTHGDSPSE ALIGPLGQVK
     LTVWYHSDEQ KLISIIHSCR ALRQNGRDLP DPYVSVLLLP DKNRGTKRKT SQKKRTLNPE
     FNERFEWDLP LDGTLRRKLD VSVKSNSSFM SRERELLGKV QLDLAEIDLS QGAAQWYDLI
     DDRDKGGS
//