EST2A_XENLA
ID EST2A_XENLA Reviewed; 872 AA.
AC Q5FWL4;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Extended synaptotagmin-2-A;
DE Short=E-Syt2-A;
GN Name=esyt2-a; Synonyms=fam62b-a;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Egg;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Tethers the endoplasmic reticulum to the cell membrane and
CC promotes the formation of appositions between the endoplasmic reticulum
CC and the cell membrane. Binds glycerophospholipids in a barrel-like
CC domain and may play a role in cellular lipid transport (By similarity).
CC Plays a role in the rapid internalization of fgfr1 that has been
CC activated by fgf1 binding; this occurs most likely via the AP-2
CC complex. Required for normal fgf signaling and the activation of
CC downstream signaling cascades via its role in the internalization of
CC activated fgfr1. Required for normal embryonic development via its role
CC in fgf signaling and the downstream regulation of t/xBRA expression (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with fgfr1 that has been activated by fgf1 binding.
CC Interacts (via C2 domains) with the AP-2 complex (via an alpha
CC subunit). Identified in a complex with the AP-2 complex and fgfr1 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q7ZWU7};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q7ZWU7}. Endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:A0FGR8}; Multi-pass membrane
CC protein {ECO:0000255}. Note=Localizes to endoplasmic reticulum-plasma
CC membrane contact sites (EPCS). Recruited to the cell membrane via the
CC third C2 domain (By similarity). {ECO:0000250|UniProtKB:A0FGR8}.
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 location at the cell membrane (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: The SMP-LTD domain is a barrel-like domain that binds
CC glycerophospholipids in its interior; can bind two lipid molecules
CC simultaneously. Binds a variety of lipids, including
CC phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol
CC (By similarity). {ECO:0000250|UniProtKB:A0FGR8}.
CC -!- SIMILARITY: Belongs to the extended synaptotagmin family.
CC {ECO:0000305}.
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DR EMBL; BC089293; AAH89293.1; -; mRNA.
DR RefSeq; NP_001089260.1; NM_001095791.1.
DR AlphaFoldDB; Q5FWL4; -.
DR SMR; Q5FWL4; -.
DR DNASU; 734307; -.
DR GeneID; 734307; -.
DR KEGG; xla:734307; -.
DR CTD; 734307; -.
DR Xenbase; XB-GENE-6251472; esyt2.S.
DR OrthoDB; 52746at2759; -.
DR Proteomes; UP000186698; Chromosome 6S.
DR Bgee; 734307; Expressed in stomach and 19 other tissues.
DR GO; GO:0140268; C:endoplasmic reticulum-plasma membrane contact site; ISS:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031227; C:intrinsic component of endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0044232; C:organelle membrane contact site; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0031210; F:phosphatidylcholine binding; ISS:UniProtKB.
DR GO; GO:0008429; F:phosphatidylethanolamine binding; ISS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
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 SMART; SM00239; C2; 3.
DR SUPFAM; SSF49562; SSF49562; 3.
DR PROSITE; PS50004; C2; 3.
DR PROSITE; PS51847; SMP; 1.
PE 2: Evidence at transcript level;
KW Calcium; Cell membrane; Endocytosis; Endoplasmic reticulum;
KW Lipid transport; Lipid-binding; Membrane; Metal-binding;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..872
FT /note="Extended synaptotagmin-2-A"
FT /id="PRO_0000278260"
FT TOPO_DOM 1..31
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 32..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 53..55
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..76
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 77..872
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 119..298
FT /note="SMP-LTD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01194"
FT DOMAIN 297..417
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 442..588
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 737..859
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 608..711
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 784..791
FT /note="Required for phosphatidylinositol 4,5-bisphosphate-
FT dependent location at the cell membrane"
FT /evidence="ECO:0000250"
FT COMPBIAS 631..649
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 661..699
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 328
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 329
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 329
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 341
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 388
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 388
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 389
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 390
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 390
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 390
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 392
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 394
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 395
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
SQ SEQUENCE 872 AA; 98080 MW; D920BB6013DD505F CRC64;
MSSESSAEKG PPPSPAENVQ PGVPPAAEEP GMISVDIAGL FYQFSKTFIL IFPVYVLGYF
GLSFSWLLIA LVLLLWWRRN KGNKNSRLYR ALAFLENEEK SVKHHIASTD LPAWVHFPDI
ERAEWLNKTV KHMWPYICQF IEKLFRETIE PAVRGANAHL STFNFTKIDM GSQPLRINGV
KVYTENVDKR QIILDLQISF VGETEIDLEV KRYFCRAGVK SIQLHGTMRV ILEPLIGDVP
IVGALSIFFL RKPLLEINWT GLTNMLDMPG LNGLSDTIIL DIISNYLVLP NRITVPLVSD
VQIAQLRFPI PKGVLRIHFL EAQDLMWKDT YMKGLVKGKS DPYGVVRLGN QVFQSKVIKE
NLNPKWNEVY EALVHEHPGQ ELEIELFDED TDKDDFLGSL LIDLVEVEKE RVVDEWFSLD
EATSGKLHLK LEWLTPNSTT DNLDQVLKSI KADKDQANDG LSSALLILYL DSARSLPNNP
LEINHDGMKK AAVEKAKKAG KKIGSSPNPY VLFSVGHAVQ ESKVKYKTAE PLWEQTFTFF
VHNPKRQDLE VEVKDENHQS SMGNLKIPLS QILASEDLTM NQRFHLNNSG PNTSLKMKIA
LRILHVDKPV RSPDEQHTSQ VKRPSIFKGK QPPTPQMPSP SPAVAHKPPP TPKLETNKKP
ENGNKGTPPS ASPKSPTELH QSSSSLSGSS FTYSPSHLPA KEPTPSIASD ISLPVATQEL
RERLRQLQNG TTLGQSPLGQ IQLTIRHSSQ RNKLMVVVHS CRNLIAFSET GSDPYVRIYL
LPDKRRSGRR KTHVYKKTLN PIYDQTFEFS VSLPELQRRT LDIAVKHSGG FLSRDKGLLG
KLLLELNTED AAKGWTQWYD LTEDGTRPAV SS
