SYT4_MOUSE
ID SYT4_MOUSE Reviewed; 425 AA.
AC P40749; Q3UFC1; Q8BGH3; Q8BRL6;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2003, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Synaptotagmin-4;
DE AltName: Full=Synaptotagmin IV;
DE Short=SytIV;
GN Name=Syt4; Synonyms=Syt3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=8058779; DOI=10.1073/pnas.91.17.8195;
RA Hilbush B.S., Morgan J.I.;
RT "A third synaptotagmin gene, Syt3, in the mouse.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:8195-8199(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RC TISSUE=Brain cortex, Medulla oblongata, Pancreas, Spinal ganglion, and
RC Sympathetic ganglion;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-135, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION.
RX PubMed=29166604; DOI=10.1016/j.celrep.2017.10.084;
RA Bharat V., Siebrecht M., Burk K., Ahmed S., Reissner C.,
RA Kohansal-Nodehi M., Steubler V., Zweckstetter M., Ting J.T., Dean C.;
RT "Capture of Dense Core Vesicles at Synapses by JNK-Dependent
RT Phosphorylation of Synaptotagmin-4.";
RL Cell Rep. 21:2118-2133(2017).
CC -!- FUNCTION: Synaptotagmin family member which does not bind Ca(2+). Plays
CC a role in dendrite formation by melanocytes (By similarity).
CC {ECO:0000250|UniProtKB:P50232, ECO:0000250|UniProtKB:Q9H2B2}.
CC -!- FUNCTION: Synaptotagmin family member which does not bind Ca(2+) (By
CC similarity). Involved in neuronal dense core vesicles (DCVs) mobility
CC through its interaction with KIF1A. Upon increased neuronal activity,
CC phosphorylation by MAPK8/JNK1 destabilizes the interaction with KIF1A
CC and captures DCVs to synapses (PubMed:29166604). Plays a role in
CC dendrite formation by melanocytes (By similarity).
CC {ECO:0000250|UniProtKB:P50232, ECO:0000250|UniProtKB:Q9H2B2,
CC ECO:0000269|PubMed:29166604}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with KIF1A; the interaction increases in presence of
CC calcium and decreases when SYT4 is phosphorylated at Ser-135.
CC {ECO:0000250|UniProtKB:P50232}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, neuronal
CC dense core vesicle membrane {ECO:0000250|UniProtKB:P50232}; Single-pass
CC membrane protein {ECO:0000250|UniProtKB:P50232}.
CC -!- TISSUE SPECIFICITY: Expressed in many regions of the nervous system but
CC is undetectable in extra neural tissues (PubMed:8058779).
CC {ECO:0000269|PubMed:8058779}.
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:0000250|UniProtKB:P50232}.
CC -!- PTM: Phosphorylation at Ser-135 by MAPK8/JNK1 reduces interaction with
CC KIF1A and neuronal dense core vesicles mobility.
CC {ECO:0000250|UniProtKB:P50232}.
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
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DR EMBL; U10355; AAA20971.1; -; mRNA.
DR EMBL; AK032106; BAC27705.1; -; mRNA.
DR EMBL; AK043985; BAC31726.1; -; mRNA.
DR EMBL; AK050515; BAC34301.1; -; mRNA.
DR EMBL; AK083960; BAC39080.1; -; mRNA.
DR EMBL; AK148681; BAE28640.1; -; mRNA.
DR EMBL; BC058208; AAH58208.1; -; mRNA.
DR CCDS; CCDS29109.1; -.
DR RefSeq; NP_033334.2; NM_009308.3.
DR AlphaFoldDB; P40749; -.
DR SMR; P40749; -.
DR BioGRID; 203614; 4.
DR STRING; 10090.ENSMUSP00000025110; -.
DR iPTMnet; P40749; -.
DR PhosphoSitePlus; P40749; -.
DR MaxQB; P40749; -.
DR PaxDb; P40749; -.
DR PRIDE; P40749; -.
DR ProteomicsDB; 254799; -.
DR Antibodypedia; 22400; 390 antibodies from 30 providers.
DR DNASU; 20983; -.
DR Ensembl; ENSMUST00000025110; ENSMUSP00000025110; ENSMUSG00000024261.
DR GeneID; 20983; -.
DR KEGG; mmu:20983; -.
DR UCSC; uc008ehy.1; mouse.
DR CTD; 6860; -.
DR MGI; MGI:101759; Syt4.
DR VEuPathDB; HostDB:ENSMUSG00000024261; -.
DR eggNOG; KOG1028; Eukaryota.
DR GeneTree; ENSGT00940000159026; -.
DR HOGENOM; CLU_023008_7_3_1; -.
DR InParanoid; P40749; -.
DR OMA; DFPRRQI; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; P40749; -.
DR TreeFam; TF315600; -.
DR BioGRID-ORCS; 20983; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Syt3; mouse.
DR PRO; PR:P40749; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; P40749; protein.
DR Bgee; ENSMUSG00000024261; Expressed in cerebellum lobe and 131 other tissues.
DR Genevisible; P40749; MM.
DR GO; GO:0097449; C:astrocyte projection; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030424; C:axon; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030425; C:dendrite; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031045; C:dense core granule; IDA:ParkinsonsUK-UCL.
DR GO; GO:0070382; C:exocytic vesicle; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005794; C:Golgi apparatus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016021; C:integral component of membrane; TAS:UniProtKB.
DR GO; GO:0099066; C:integral component of neuronal dense core vesicle membrane; IDA:SynGO.
DR GO; GO:0098675; C:intrinsic component of neuronal dense core vesicle membrane; ISS:UniProtKB.
DR GO; GO:1990742; C:microvesicle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0044306; C:neuron projection terminus; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:ParkinsonsUK-UCL.
DR GO; GO:0098992; C:neuronal dense core vesicle; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0098794; C:postsynapse; NAS:SynGO.
DR GO; GO:0098793; C:presynapse; NAS:SynGO-UCL.
DR GO; GO:0030667; C:secretory granule membrane; ISO:MGI.
DR GO; GO:0036477; C:somatodendritic compartment; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0031982; C:vesicle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005509; F:calcium ion binding; IDA:MGI.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030276; F:clathrin binding; ISO:MGI.
DR GO; GO:0001786; F:phosphatidylserine binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0000149; F:SNARE binding; ISO:MGI.
DR GO; GO:0019905; F:syntaxin binding; ISO:MGI.
DR GO; GO:0017075; F:syntaxin-1 binding; ISO:MGI.
DR GO; GO:0030348; F:syntaxin-3 binding; ISO:MGI.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0071277; P:cellular response to calcium ion; IBA:GO_Central.
DR GO; GO:0099519; P:dense core granule cytoskeletal transport; IMP:UniProtKB.
DR GO; GO:0007613; P:memory; IMP:ParkinsonsUK-UCL.
DR GO; GO:0045955; P:negative regulation of calcium ion-dependent exocytosis; ISO:MGI.
DR GO; GO:0033604; P:negative regulation of catecholamine secretion; ISO:MGI.
DR GO; GO:1905414; P:negative regulation of dense core granule exocytosis; ISO:MGI.
DR GO; GO:0046929; P:negative regulation of neurotransmitter secretion; ISO:MGI.
DR GO; GO:0050709; P:negative regulation of protein secretion; IMP:SynGO-UCL.
DR GO; GO:1905433; P:negative regulation of retrograde trans-synaptic signaling by neuropeptide; IMP:SynGO-UCL.
DR GO; GO:0048174; P:negative regulation of short-term neuronal synaptic plasticity; IMP:ParkinsonsUK-UCL.
DR GO; GO:2000301; P:negative regulation of synaptic vesicle exocytosis; IMP:SynGO-UCL.
DR GO; GO:0031339; P:negative regulation of vesicle fusion; ISO:MGI.
DR GO; GO:0007269; P:neurotransmitter secretion; IDA:MGI.
DR GO; GO:1903861; P:positive regulation of dendrite extension; ISO:MGI.
DR GO; GO:1905415; P:positive regulation of dense core granule exocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0014049; P:positive regulation of glutamate secretion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0014059; P:regulation of dopamine secretion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0030100; P:regulation of endocytosis; IMP:ParkinsonsUK-UCL.
DR GO; GO:0099161; P:regulation of presynaptic dense core granule exocytosis; IDA:SynGO.
DR GO; GO:0031338; P:regulation of vesicle fusion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0061792; P:secretory granule maturation; ISO:MGI.
DR GO; GO:0048489; P:synaptic vesicle transport; TAS:UniProtKB.
DR GO; GO:0099183; P:trans-synaptic signaling by BDNF, modulating synaptic transmission; IDA:SynGO.
DR GO; GO:0006906; P:vesicle fusion; IBA:GO_Central.
DR GO; GO:0061782; P:vesicle fusion with vesicle; ISO:MGI.
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; IPR028683; SYT4.
DR PANTHER; PTHR10024:SF114; PTHR10024:SF114; 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; Cytoplasmic vesicle; Differentiation; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..425
FT /note="Synaptotagmin-4"
FT /id="PRO_0000183949"
FT TOPO_DOM 1..16
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 38..425
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 153..274
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 287..420
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 127..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
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 MOD_RES 135
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 70
FT /note="K -> Q (in Ref. 1; AAA20971)"
FT /evidence="ECO:0000305"
FT CONFLICT 85
FT /note="A -> T (in Ref. 1; AAA20971)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="D -> G (in Ref. 1; AAA20971)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="D -> N (in Ref. 2; BAC31726)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 425 AA; 47659 MW; 9A01144898CDFCEB CRC64;
MAPITTSRVE FDEIPTVVGI FSAFGLVFTV SLFAWICCQR RSAKSNKTPP YKFVHVLKGV
DIYPENLSSK KKFGGDDKSE VKGKAALPNL SLHLDLEKRD LNGNFPKANP KAGSSSDLEN
VTPKLFTETE KEANSPESLK SSTSLTSEEK QEKLGTLFLS LEYNFEKKAF VVNIKEAQGL
PAMDEQSMTS DPYIKMTILP EKKHRVKTRV LRKTLDPVFD ETFTFYGIPY PHIQELSLHF
TVLSFDRFSR DDVIGEVLIP LSGIELSDGK MLMTREIIKR NAKKSSGRGE LLVSLCYQST
TNTLTVVVLK ARHLPKSDVS GLSDPYVKVN LYHAKKRISK KKTHVKKCTP NAVFNELFVF
DIPCESLEEI SVEFLVLDSE RGSRNEVIGR LVLGATAEGS GGGHWKEICD FPRRQIAKWH
MLCDG
