SYT11_RAT
ID SYT11_RAT Reviewed; 430 AA.
AC O08835; Q925B6;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Synaptotagmin-11 {ECO:0000305};
DE AltName: Full=Synaptotagmin XI;
DE Short=SytXI;
GN Name=Syt11 {ECO:0000312|RGD:62042};
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], TISSUE SPECIFICITY, MUTAGENESIS OF SER-247, AND
RP FUNCTION.
RC TISSUE=Brain;
RX PubMed=9162066; DOI=10.1074/jbc.272.22.14314;
RA von Poser C., Ichtchenko K., Shao X., Rizo J., Suedhof T.C.;
RT "The evolutionary pressure to inactivate. A subclass of synaptotagmins with
RT an amino acid substitution that abolishes Ca2+ binding.";
RL J. Biol. Chem. 272:14314-14319(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shin O.-H., von Poser C., Ichtchenko K., Shao X., Rizo J., Suedhof T.C.;
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH AGO2 AND SND1.
RX PubMed=24882364; DOI=10.1016/j.febslet.2014.05.031;
RA Milochau A., Lagree V., Benassy M.N., Chaignepain S., Papin J.,
RA Garcia-Arcos I., Lajoix A., Monterrat C., Coudert L., Schmitter J.M.,
RA Ochoa B., Lang J.;
RT "Synaptotagmin 11 interacts with components of the RNA-induced silencing
RT complex RISC in clonal pancreatic beta-cells.";
RL FEBS Lett. 588:2217-2222(2014).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF 345-LYS-LYS-346.
RX PubMed=26589353; DOI=10.15252/embr.201540689;
RA Wang C., Wang Y., Hu M., Chai Z., Wu Q., Huang R., Han W., Zhang C.X.,
RA Zhou Z.;
RT "Synaptotagmin-11 inhibits clathrin-mediated and bulk endocytosis.";
RL EMBO Rep. 17:47-63(2016).
RN [5]
RP UBIQUITINATED, DOMAIN, AND FUNCTION.
RX PubMed=29311685; DOI=10.1038/s41467-017-02593-y;
RA Wang C., Kang X., Zhou L., Chai Z., Wu Q., Huang R., Xu H., Hu M., Sun X.,
RA Sun S., Li J., Jiao R., Zuo P., Zheng L., Yue Z., Zhou Z.;
RT "Synaptotagmin-11 is a critical mediator of parkin-linked neurotoxicity and
RT Parkinson's disease-like pathology.";
RL Nat. Commun. 9:81-81(2018).
RN [6]
RP INTERACTION WITH KIF1A.
RX PubMed=30021165; DOI=10.1016/j.celrep.2018.06.071;
RA Stucchi R., Plucinska G., Hummel J.J.A., Zahavi E.E., Guerra San Juan I.,
RA Klykov O., Scheltema R.A., Altelaar A.F.M., Hoogenraad C.C.;
RT "Regulation of KIF1A-Driven Dense Core Vesicle Transport: Ca2+/CaM Controls
RT DCV Binding and Liprin-alpha/TANC2 Recruits DCVs to Postsynaptic Sites.";
RL Cell Rep. 24:685-700(2018).
CC -!- FUNCTION: Synaptotagmin family member involved in vesicular and
CC membrane trafficking which does not bind Ca(2+) (PubMed:9162066).
CC Inhibits clathrin-mediated and bulk endocytosis in neurons, functions
CC to ensure precision in vesicle retrieval (PubMed:29311685,
CC PubMed:26589353). Plays an important role in dopamine transmission by
CC regulating endocytosis and the vesicle-recycling process
CC (PubMed:29311685). Essential component of a neuronal vesicular
CC trafficking pathway that differs from the synaptic vesicle trafficking
CC pathway but is crucial for development and synaptic plasticity. In
CC macrophages and microglia, inhibits the conventional cytokine
CC secretion, of at least IL6 and TNF, and phagocytosis. In astrocytes,
CC regulates lysosome exocytosis, mechanism required for the repair of
CC injured astrocyte cell membrane (By similarity). Required for the
CC ATP13A2-mediated regulation of the autophagy-lysosome pathway (By
CC similarity). {ECO:0000250|UniProtKB:Q9BT88,
CC ECO:0000250|UniProtKB:Q9R0N3, ECO:0000269|PubMed:26589353,
CC ECO:0000269|PubMed:29311685, ECO:0000269|PubMed:9162066}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Homodimer. Can also form heterodimers. Interacts with PRKN (By
CC similarity). Interacts (via C2 2 domain) with AGO2 and SND1; the
CC interaction with SND1 is direct (PubMed:24882364). Interacts with
CC KIF1A; the interaction increases in presence of calcium
CC (PubMed:30021165). {ECO:0000250|UniProtKB:Q9BT88,
CC ECO:0000269|PubMed:24882364, ECO:0000269|PubMed:30021165}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:Q9R0N3}; Single-pass membrane protein
CC {ECO:0000305}. Perikaryon {ECO:0000250|UniProtKB:Q9R0N3}. Golgi
CC apparatus, trans-Golgi network membrane {ECO:0000250|UniProtKB:Q9R0N3};
CC Single-pass membrane protein {ECO:0000250|UniProtKB:Q9R0N3}. Recycling
CC endosome membrane {ECO:0000269|PubMed:26589353}; Single-pass membrane
CC protein {ECO:0000305}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9R0N3}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9R0N3}. Cytoplasmic vesicle, phagosome
CC {ECO:0000250|UniProtKB:Q9R0N3}. Cell projection, axon
CC {ECO:0000269|PubMed:26589353}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q9R0N3}. Postsynaptic density
CC {ECO:0000250|UniProtKB:Q9R0N3}. Cytoplasmic vesicle, clathrin-coated
CC vesicle membrane {ECO:0000269|PubMed:26589353}; Single-pass membrane
CC protein {ECO:0000305}. Perikaryon {ECO:0000269|PubMed:26589353}.
CC Note=Localized in vesicles that travels in axonal and dendritic shafts
CC in both anterograde and retrograde directions. In macrophages and
CC microglia, recruited in phagosomes at early stages of phagocytosis.
CC {ECO:0000250|UniProtKB:Q9R0N3}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and at lower levels in
CC other tissues. {ECO:0000269|PubMed:9162066}.
CC -!- DOMAIN: The second C2 domain/C2B is required for the inhibitory role in
CC both clathrin-mediated and bulk endocytosis (PubMed:26589353,
CC PubMed:29311685). The transmembrane domain and the first C2 domain/C2A
CC are critical for the inhibitory role in clathrin-mediated endocytosis
CC or bulk endocytosis, respectively (PubMed:26589353).
CC {ECO:0000269|PubMed:26589353, ECO:0000269|PubMed:29311685}.
CC -!- DOMAIN: Unlike in other synaptotagmin family members, the first C2
CC domain/C2A does not bind Ca(2+) neither mediates Ca(2+)-dependent
CC phospholipid binding. An aspartate-to-serine substitution in this
CC domain inactivates Ca(2+)/phospho-lipid binding.
CC {ECO:0000269|PubMed:9162066}.
CC -!- PTM: Ubiquitinated, at least by PRKN, and targeted to the proteasome
CC complex for degradation (PubMed:29311685). Ubiquitination is inhibited
CC by ATP13A2 (By similarity). {ECO:0000250|UniProtKB:Q9BT88,
CC ECO:0000269|PubMed:29311685}.
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
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DR EMBL; AF000423; AAB58344.1; -; mRNA.
DR EMBL; AF375465; AAK56960.1; -; mRNA.
DR RefSeq; XP_006232810.1; XM_006232748.1.
DR AlphaFoldDB; O08835; -.
DR SMR; O08835; -.
DR BioGRID; 248858; 1.
DR STRING; 10116.ENSRNOP00000027474; -.
DR iPTMnet; O08835; -.
DR PhosphoSitePlus; O08835; -.
DR PaxDb; O08835; -.
DR PRIDE; O08835; -.
DR GeneID; 60568; -.
DR UCSC; RGD:62042; rat.
DR CTD; 23208; -.
DR RGD; 62042; Syt11.
DR VEuPathDB; HostDB:ENSRNOG00000020279; -.
DR eggNOG; KOG1028; Eukaryota.
DR HOGENOM; CLU_023008_7_3_1; -.
DR InParanoid; O08835; -.
DR OMA; LQVINHD; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; O08835; -.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR PRO; PR:O08835; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000020279; Expressed in frontal cortex and 20 other tissues.
DR Genevisible; O08835; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:ParkinsonsUK-UCL.
DR GO; GO:0044297; C:cell body; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030665; C:clathrin-coated vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB.
DR GO; GO:0060076; C:excitatory synapse; IDA:ParkinsonsUK-UCL.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0060077; C:inhibitory synapse; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; IDA:SynGO.
DR GO; GO:0030285; C:integral component of synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ParkinsonsUK-UCL.
DR GO; GO:0001891; C:phagocytic cup; ISO:RGD.
DR GO; GO:0045335; C:phagocytic vesicle; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR GO; GO:0014069; C:postsynaptic density; IDA:ParkinsonsUK-UCL.
DR GO; GO:0098793; C:presynapse; IDA:ParkinsonsUK-UCL.
DR GO; GO:0048787; C:presynaptic active zone membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0055037; C:recycling endosome; ISS:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0008021; C:synaptic vesicle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043195; C:terminal bouton; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0031982; C:vesicle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0048487; F:beta-tubulin binding; ISO:RGD.
DR GO; GO:0030276; F:clathrin binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central.
DR GO; GO:0000149; F:SNARE binding; ISO:RGD.
DR GO; GO:0031369; F:translation initiation factor binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0006914; P:autophagy; ISS:UniProtKB.
DR GO; GO:1990927; P:calcium ion regulated lysosome exocytosis; ISO:RGD.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; IBA:GO_Central.
DR GO; GO:0071277; P:cellular response to calcium ion; IBA:GO_Central.
DR GO; GO:0051650; P:establishment of vesicle localization; ISS:UniProtKB.
DR GO; GO:0007612; P:learning; ISS:UniProtKB.
DR GO; GO:0007613; P:memory; ISS:UniProtKB.
DR GO; GO:1905469; P:negative regulation of clathrin-coated pit assembly; IMP:ParkinsonsUK-UCL.
DR GO; GO:1900186; P:negative regulation of clathrin-dependent endocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0033602; P:negative regulation of dopamine secretion; IDA:UniProtKB.
DR GO; GO:0045806; P:negative regulation of endocytosis; IDA:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:1905154; P:negative regulation of membrane invagination; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903979; P:negative regulation of microglial cell activation; ISS:UniProtKB.
DR GO; GO:0050765; P:negative regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:1900243; P:negative regulation of synaptic vesicle endocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0001778; P:plasma membrane repair; ISO:RGD.
DR GO; GO:1905171; P:positive regulation of protein localization to phagocytic vesicle; ISO:RGD.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IBA:GO_Central.
DR GO; GO:1900424; P:regulation of defense response to bacterium; ISO:RGD.
DR GO; GO:0014059; P:regulation of dopamine secretion; IBA:GO_Central.
DR GO; GO:0009611; P:response to wounding; ISO:RGD.
DR GO; GO:0006906; P:vesicle fusion; IBA:GO_Central.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR Gene3D; 2.60.40.150; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR001565; Synaptotagmin.
DR InterPro; IPR028699; SYT11.
DR PANTHER; PTHR10024:SF115; PTHR10024:SF115; 1.
DR Pfam; PF00168; C2; 2.
DR PRINTS; PR00399; SYNAPTOTAGMN.
DR SMART; SM00239; C2; 2.
DR SUPFAM; SSF49562; SSF49562; 2.
DR PROSITE; PS50004; C2; 2.
PE 1: Evidence at protein level;
KW Calcium; Cell projection; Cytoplasmic vesicle; Endosome; Golgi apparatus;
KW Lysosome; Membrane; Metal-binding; Phosphoprotein; Reference proteome;
KW Repeat; Synapse; Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..430
FT /note="Synaptotagmin-11"
FT /id="PRO_0000183971"
FT TOPO_DOM 1..15
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 16..36
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 37..430
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 156..278
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 290..425
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 132..154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 136..154
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 249
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 255
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R0N3"
FT MUTAGEN 247
FT /note="S->D: Restores Ca(2+)-binding and Ca(2+)-dependent
FT phospholipid binding."
FT /evidence="ECO:0000269|PubMed:9162066"
FT MUTAGEN 345..346
FT /note="KK->AA: Loss of inhibition of clathrin-mediated and
FT bulk endocytosis."
FT /evidence="ECO:0000269|PubMed:26589353"
FT CONFLICT 74
FT /note="K -> E (in Ref. 1; AAB58344)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 430 AA; 48268 MW; FEEB06702BAC2AFB CRC64;
MAEITNIRPS FDVSPVAAGL IGASVLVVCV SVTVFVWTCC HQQAEKKHKT PPYKFIHMLK
GISIYPETLS NKKKIIKVRR DKDGSHRESG RGNLLVNAES GLLSHDRDPR GPSPASCIDQ
LPIKRDYGEE LRSPMTSLTP GESKPTSPSS PEEDVMLGSL TFSVDYNFPK KALVVTIQEA
HGLPVMDGQT QGSDPYIKMT ILPDKRHRVK TRVLRKTLDP VFDETFTFYG IPYSQLQDLV
LHFLVLSFDR FSRDDVIGEV MVPLAGVDPS TGKVQLTRDI IKRNIQKCIS RGELQVSLSY
QPVAQRMTVV VLKARHLPKM DITGLSGNPY VKVNVYYGRK RIAKKKTHVK KCTLNPIFNE
SFIYDIPTDL LPDISIEFLV IDFDRTTKNE VVGRLILGAH SVTTSGAEHW REVCESPRKP
VAKWHSLSEY
