EST2B_XENLA
ID EST2B_XENLA Reviewed; 876 AA.
AC Q7ZWU7;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Extended synaptotagmin-2-B;
DE Short=E-Syt2-B;
GN Name=esyt2-b; Synonyms=fam62b-b;
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=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND DOMAIN.
RX PubMed=20833364; DOI=10.1016/j.devcel.2010.08.007;
RA Jean S., Mikryukov A., Tremblay M.G., Baril J., Guillou F., Bellenfant S.,
RA Moss T.;
RT "Extended-synaptotagmin-2 mediates FGF receptor endocytosis and ERK
RT activation in vivo.";
RL Dev. Cell 19:426-439(2010).
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.
CC {ECO:0000250, ECO:0000269|PubMed:20833364}.
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.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20833364};
CC Peripheral membrane protein {ECO:0000269|PubMed:20833364}. 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 -!- DEVELOPMENTAL STAGE: Detected throughout embryonic development. In late
CC gastrula and neurula stages, mainly expressed in head and dorsolateral
CC mesoderm, and in eye, cranial neural crest and somites at later stages.
CC {ECO:0000269|PubMed:20833364}.
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 (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. {ECO:0000250, ECO:0000269|PubMed:20833364}.
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 -!- DISRUPTION PHENOTYPE: Morpholino-mediated knock-down causes severe
CC trunk shortening, disruption of somatic muscle formation and impairs
CC the expression of the mesodermal marker t/xBRA, similar to the effects
CC of inhibition of fgf signaling. {ECO:0000269|PubMed:20833364}.
CC -!- SIMILARITY: Belongs to the extended synaptotagmin family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC046701; AAH46701.1; -; mRNA.
DR RefSeq; NP_001080586.1; NM_001087117.1.
DR AlphaFoldDB; Q7ZWU7; -.
DR SMR; Q7ZWU7; -.
DR GeneID; 380278; -.
DR KEGG; xla:380278; -.
DR CTD; 380278; -.
DR Xenbase; XB-GENE-5932792; esyt2.L.
DR OrthoDB; 52746at2759; -.
DR Proteomes; UP000186698; Chromosome 6L.
DR Bgee; 380278; Expressed in spleen 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..876
FT /note="Extended synaptotagmin-2-B"
FT /id="PRO_0000278261"
FT TOPO_DOM 1..35
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 36..56
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..59
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 81..876
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 123..302
FT /note="SMP-LTD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01194"
FT DOMAIN 301..421
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 446..592
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 741..863
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 614..714
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 788..795
FT /note="Required for phosphatidylinositol 4,5-bisphosphate-
FT dependent location at the cell membrane"
FT /evidence="ECO:0000250"
FT COMPBIAS 635..653
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 665..701
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 332
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 333
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 333
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
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 392
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 392
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 393
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 394
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 394
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
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 396
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
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 399
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
SQ SEQUENCE 876 AA; 98434 MW; 55560141069CA82E CRC64;
MASESGAEKG PPTTPAENGQ PGVPIAAAVA ADEQGMISVD IAGLFYQFSK TFILIFPVYV
LGYFGLSFSW LLIALVLLLW WRRNKGNKNS RLYRALAFLE TEEKSVKHHI ASIDLPAWVH
FPDIERAEWL NKTVKHMWPY ICQFIEKLFR ETIEPAVRGA NAHLSTFSFT KIDMGSQPLR
INGVKVYTEN VDKRQIILDL QISFVGETEI DLEVKRYFCR AGVKSIQLHG TMRVILEPLI
GDVPIVGALS IFFLRKPLLE INWTGLTNML DMPGLNGLSD TIILDIISNY LVLPNRITVP
LVSDVQIAQL RFPIPKGVLR IHFLEAQDLM WKDTYMKGLV KGKSDPYGVV RLGNQVFQSK
VIKENLNPKW NEVYEALVHE HPGQELEIEL FDEDTDKDDF LGSLLIDLVE VEKERVVDEW
FTLDEATSGK LHLKLEWLTP KSTTENLDQV LKSIKADKDQ ANDGLSAALL ILYLDSARSL
PNNPLEINHD GMKKAAVEKA KKAGKKIGSS PNPYVLFSVG HTVQESKVKY KTAEPVWEQT
FTFFVHNPKR QDLEVEVKDE NHQNSMGNIK IPLSQILASE DLTLNQRFHL NNSGPNSSLK
MKIALRILHV EKPVRSPDEQ HTSQVKRPSI FKGKQPPTPQ MPAPSPAVAH KPPPTPKLET
NKKLENGNKS STPSASPKRP TELHKSSSSL SGSSFTYSPP HLPTKEPTPS IASDISLPVA
TQELRERLRQ LQNGTTLGQS PLGQIQLTIR HSSQRNKLMV VVHSCRNLIA FSEEGSDPYV
RIYLLPDKRR SGRRKTHVHK RTLNPIYDQT FEFSVSLADL QRRTLDVAVK NGGGFLFREK
GLLGKLLLEI NTEDAAKGWT QWFDLTEDGT RAAASS
