SYT2_HUMAN
ID SYT2_HUMAN Reviewed; 419 AA.
AC Q8N9I0; Q496K5; Q8NBE5;
DT 19-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Synaptotagmin-2 {ECO:0000305};
DE AltName: Full=Synaptotagmin II {ECO:0000312|HGNC:HGNC:11510};
DE Short=SytII {ECO:0000250|UniProtKB:P29101};
GN Name=SYT2 {ECO:0000312|HGNC:HGNC:11510};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 INTERACTION WITH STON2.
RX PubMed=11381094; DOI=10.1083/jcb.153.5.1111;
RA Martina J.A., Bonangelino C.J., Aguilar R.C., Bonifacino J.S.;
RT "Stonin 2: an adaptor-like protein that interacts with components of the
RT endocytic machinery.";
RL J. Cell Biol. 153:1111-1120(2001).
RN [4]
RP INTERACTION WITH SCAMP5.
RX PubMed=19234194; DOI=10.4049/jimmunol.0802002;
RA Han C., Chen T., Yang M., Li N., Liu H., Cao X.;
RT "Human SCAMP5, a novel secretory carrier membrane protein, facilitates
RT calcium-triggered cytokine secretion by interaction with SNARE machinery.";
RL J. Immunol. 182:2986-2996(2009).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23999003; DOI=10.1016/j.jdermsci.2013.07.010;
RA Yoo J.C., Lim T.Y., Park J.S., Hah Y.S., Park N., Hong S.G., Park J.Y.,
RA Yoon T.J.;
RT "SYT14L, especially its C2 domain, is involved in regulating melanocyte
RT differentiation.";
RL J. Dermatol. Sci. 72:246-251(2013).
RN [6]
RP INVOLVEMENT IN CMS7A, AND VARIANTS CMS7A ALA-307 AND LEU-308.
RX PubMed=25192047; DOI=10.1016/j.ajhg.2014.08.007;
RA Herrmann D.N., Horvath R., Sowden J.E., Gonzales M., Sanchez-Mejias A.,
RA Guan Z., Whittaker R.G., Almodovar J.L., Lane M., Bansagi B., Pyle A.,
RA Boczonadi V., Lochmuller H., Griffin H., Chinnery P.F., Lloyd T.E.,
RA Littleton J.T., Zuchner S.;
RT "Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-
RT eaton myasthenic syndrome and nonprogressive motor neuropathy.";
RL Am. J. Hum. Genet. 95:332-339(2014).
RN [7]
RP INVOLVEMENT IN CMS7B.
RX PubMed=32250532; DOI=10.1002/ajmg.a.61579;
RA Maselli R.A., van der Linden H. Jr., Ferns M.;
RT "Recessive congenital myasthenic syndrome caused by a homozygous mutation
RT in SYT2 altering a highly conserved C-terminal amino acid sequence.";
RL Am. J. Med. Genet. A 182:1744-1749(2020).
RN [8]
RP VARIANTS CMS7B 269-GLU--LYS-419 DEL AND 309-TYR--LYS-419 DEL.
RX PubMed=32776697; DOI=10.1002/ajmg.a.61765;
RA Donkervoort S., Mohassel P., Laugwitz L., Zaki M.S., Kamsteeg E.J.,
RA Maroofian R., Chao K.R., Verschuuren-Bemelmans C.C., Horber V.,
RA Fock A.J.M., McCarty R.M., Jain M.S., Biancavilla V., McMacken G.,
RA Nalls M., Voermans N.C., Elbendary H.M., Snyder M., Cai C., Lehky T.J.,
RA Stanley V., Iannaccone S.T., Foley A.R., Lochmueller H., Gleeson J.,
RA Houlden H., Haack T.B., Horvath R., Boennemann C.G.;
RT "Biallelic loss of function variants in SYT2 cause a treatable congenital
RT onset presynaptic myasthenic syndrome.";
RL Am. J. Med. Genet. A 182:2272-2283(2020).
RN [9]
RP INVOLVEMENT IN CMS7B, AND TISSUE SPECIFICITY.
RX PubMed=33659639; DOI=10.1212/nxg.0000000000000534;
RA Bauche S., Sureau A., Sternberg D., Rendu J., Buon C., Messeant J.,
RA Boex M., Furling D., Faure J., Latypova X., Gelot A.B., Mayer M., Mary P.,
RA Whalen S., Fournier E., Cloix I., Remerand G., Laffargue F., Nougues M.C.,
RA Fontaine B., Eymard B., Isapof A., Strochlic L.;
RT "New recessive mutations in SYT2 causing severe presynaptic congenital
RT myasthenic syndromes.";
RL Neurol. Genet. 6:e534-e534(2020).
RN [10]
RP VARIANT CMS7A 361-ASP--LEU-365 DEL.
RX PubMed=33320396; DOI=10.1111/jns.12425;
RA Fionda L., Turon-Sans J., Fuentes Prior P., Bernal Noguera S.,
RA Cortes-Vicente E., Lopez-Perez M.A., Gallardo E., Rojas-Garcia R.;
RT "A new de novo SYT2 mutation presenting as distal weakness. Neuropathy or
RT neuromuscular junction dysfunction?";
RL J. Peripher. Nerv. Syst. 26:113-117(2021).
RN [11]
RP ERRATUM OF PUBMED:33320396.
RX PubMed=34151484; DOI=10.1111/jns.12441;
RA Fionda L., Turon-Sans J., Fuentes Prior P., Bernal Noguera S.,
RA Cortes-Vicente E., Lopez-Perez M.A., Gallardo E., Rojas-Garcia R.;
RL J. Peripher. Nerv. Syst. 26:237-237(2021).
RN [12]
RP VARIANT CMS7A PRO-365.
RX PubMed=34037996; DOI=10.1002/mus.27332;
RA Maselli R.A., Wei D.T., Hodgson T.S., Sampson J.B., Vazquez J., Smith H.L.,
RA Pytel P., Ferns M.;
RT "Dominant and recessive congenital myasthenic syndromes caused by SYT2
RT mutations.";
RL Muscle Nerve 64:219-224(2021).
CC -!- FUNCTION: Exhibits calcium-dependent phospholipid and inositol
CC polyphosphate binding properties (By similarity). May have a regulatory
CC role in the membrane interactions during trafficking of synaptic
CC vesicles at the active zone of the synapse (By similarity). Plays a
CC role in dendrite formation by melanocytes (PubMed:23999003).
CC {ECO:0000250|UniProtKB:P46097, ECO:0000269|PubMed:23999003}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2
CC domains. {ECO:0000250|UniProtKB:P21707};
CC -!- SUBUNIT: Homotetramer (Probable). Interacts with STON2
CC (PubMed:11381094). Interacts with SCAMP5 (PubMed:19234194). Interacts
CC with PRRT2 (By similarity). {ECO:0000250|UniProtKB:P46097,
CC ECO:0000269|PubMed:11381094, ECO:0000269|PubMed:19234194, ECO:0000305}.
CC -!- INTERACTION:
CC Q8N9I0; Q96PS8: AQP10; NbExp=3; IntAct=EBI-8032987, EBI-12820279;
CC Q8N9I0; Q12982: BNIP2; NbExp=3; IntAct=EBI-8032987, EBI-752094;
CC Q8N9I0; Q9P0B6: CCDC167; NbExp=3; IntAct=EBI-8032987, EBI-9083477;
CC Q8N9I0; O14493: CLDN4; NbExp=3; IntAct=EBI-8032987, EBI-9316372;
CC Q8N9I0; Q96MX0: CMTM3; NbExp=3; IntAct=EBI-8032987, EBI-7247651;
CC Q8N9I0; Q7L5A8: FA2H; NbExp=3; IntAct=EBI-8032987, EBI-11337888;
CC Q8N9I0; Q9BWH2: FUNDC2; NbExp=3; IntAct=EBI-8032987, EBI-714482;
CC Q8N9I0; P42858: HTT; NbExp=10; IntAct=EBI-8032987, EBI-466029;
CC Q8N9I0; P11215: ITGAM; NbExp=3; IntAct=EBI-8032987, EBI-2568251;
CC Q8N9I0; O43561-2: LAT; NbExp=3; IntAct=EBI-8032987, EBI-8070286;
CC Q8N9I0; Q13021: MALL; NbExp=3; IntAct=EBI-8032987, EBI-750078;
CC Q8N9I0; P30301: MIP; NbExp=3; IntAct=EBI-8032987, EBI-8449636;
CC Q8N9I0; Q9H115: NAPB; NbExp=3; IntAct=EBI-8032987, EBI-3921185;
CC Q8N9I0; Q8N138: ORMDL3; NbExp=3; IntAct=EBI-8032987, EBI-721750;
CC Q8N9I0; Q5VZY2: PLPP4; NbExp=3; IntAct=EBI-8032987, EBI-10485931;
CC Q8N9I0; Q01453: PMP22; NbExp=3; IntAct=EBI-8032987, EBI-2845982;
CC Q8N9I0; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-8032987, EBI-10262251;
CC Q8N9I0; P78382: SLC35A1; NbExp=3; IntAct=EBI-8032987, EBI-12870360;
CC Q8N9I0; Q96G79: SLC35A4; NbExp=3; IntAct=EBI-8032987, EBI-12363689;
CC Q8N9I0; P02787: TF; NbExp=3; IntAct=EBI-8032987, EBI-714319;
CC Q8N9I0; C9JKN6: THSD7B; NbExp=3; IntAct=EBI-8032987, EBI-17192156;
CC Q8N9I0; Q6UX40: TMEM107; NbExp=3; IntAct=EBI-8032987, EBI-12845616;
CC Q8N9I0; Q8NBD8: TMEM229B; NbExp=3; IntAct=EBI-8032987, EBI-12195227;
CC Q8N9I0; Q5TGU0: TSPO2; NbExp=3; IntAct=EBI-8032987, EBI-12195249;
CC Q8N9I0; O75379: VAMP4; NbExp=3; IntAct=EBI-8032987, EBI-744953;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000250}; Single-pass membrane protein
CC {ECO:0000250}. Cytoplasmic vesicle, secretory vesicle, chromaffin
CC granule membrane {ECO:0000250}; Single-pass membrane protein
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed at the neuromuscular junction
CC (PubMed:33659639). Expressed in melanocytes (PubMed:23999003).
CC {ECO:0000269|PubMed:23999003, ECO:0000269|PubMed:33659639}.
CC -!- DOMAIN: The first C2 domain mediates Ca(2+)-dependent phospholipid
CC binding. {ECO:0000250|UniProtKB:P46097}.
CC -!- DOMAIN: The second C2 domain mediates interaction with Stonin 2. The
CC second C2 domain mediates phospholipid and inositol polyphosphate
CC binding in a calcium-independent manner.
CC {ECO:0000250|UniProtKB:P46097}.
CC -!- DISEASE: Myasthenic syndrome, congenital, 7A, presynaptic, and distal
CC motor neuropathy, autosomal dominant (CMS7A) [MIM:616040]: A form of
CC congenital myasthenic syndrome, a group of disorders characterized by
CC failure of neuromuscular transmission, including pre-synaptic,
CC synaptic, and post-synaptic disorders that are not of autoimmune
CC origin. Clinical features are easy fatigability and muscle weakness.
CC CMS7A is an autosomal dominant, presynaptic disorder resembling
CC Lambert-Eaton myasthenic syndrome. Affected individuals have a variable
CC degree of proximal and distal limb weakness, muscle fatigue that
CC improves with rest, mild gait difficulties, and reduced or absent deep
CC tendon reflexes. {ECO:0000269|PubMed:25192047,
CC ECO:0000269|PubMed:33320396, ECO:0000269|PubMed:34037996}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Myasthenic syndrome, congenital, 7B, presynaptic, autosomal
CC recessive (CMS7B) [MIM:619461]: An autosomal recessive form of
CC congenital myasthenic syndrome, a group of disorders characterized by
CC failure of neuromuscular transmission, including pre-synaptic,
CC synaptic, and post-synaptic disorders that are not of autoimmune
CC origin. Clinical features are easy fatigability and muscle weakness.
CC CMS7B is characterized by defects at the pre-synaptic neuromuscular
CC junction and severe generalized muscle weakness apparent from birth.
CC Decreased fetal movements may be apparent in utero. Affected infants
CC have generalized hypotonia, head lag, and facial muscle weakness with
CC ptosis. Some patients may have respiratory involvement.
CC {ECO:0000269|PubMed:32250532, ECO:0000269|PubMed:32776697,
CC ECO:0000269|PubMed:33659639}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the synaptotagmin family. {ECO:0000305}.
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DR EMBL; AK090672; BAC03500.1; -; mRNA.
DR EMBL; AK094430; BAC04354.1; -; mRNA.
DR EMBL; BC100814; AAI00815.1; -; mRNA.
DR EMBL; BC100815; AAI00816.1; -; mRNA.
DR EMBL; BC100817; AAI00818.1; -; mRNA.
DR CCDS; CCDS1427.1; -.
DR RefSeq; NP_001129976.1; NM_001136504.1.
DR RefSeq; NP_796376.2; NM_177402.4.
DR RefSeq; XP_016855802.1; XM_017000313.1.
DR PDB; 6G5G; X-ray; 2.00 A; P=37-57.
DR PDBsum; 6G5G; -.
DR AlphaFoldDB; Q8N9I0; -.
DR SMR; Q8N9I0; -.
DR BioGRID; 126085; 127.
DR ELM; Q8N9I0; -.
DR IntAct; Q8N9I0; 31.
DR MINT; Q8N9I0; -.
DR STRING; 9606.ENSP00000356236; -.
DR DrugBank; DB00042; Botulinum toxin type B.
DR GlyGen; Q8N9I0; 1 site.
DR iPTMnet; Q8N9I0; -.
DR PhosphoSitePlus; Q8N9I0; -.
DR BioMuta; SYT2; -.
DR DMDM; 116242811; -.
DR EPD; Q8N9I0; -.
DR jPOST; Q8N9I0; -.
DR MassIVE; Q8N9I0; -.
DR PaxDb; Q8N9I0; -.
DR PeptideAtlas; Q8N9I0; -.
DR PRIDE; Q8N9I0; -.
DR ProteomicsDB; 72541; -.
DR Antibodypedia; 34528; 277 antibodies from 32 providers.
DR DNASU; 127833; -.
DR Ensembl; ENST00000367267.5; ENSP00000356236.1; ENSG00000143858.12.
DR Ensembl; ENST00000367268.5; ENSP00000356237.4; ENSG00000143858.12.
DR GeneID; 127833; -.
DR KEGG; hsa:127833; -.
DR MANE-Select; ENST00000367268.5; ENSP00000356237.4; NM_177402.5; NP_796376.2.
DR UCSC; uc001gye.4; human.
DR CTD; 127833; -.
DR DisGeNET; 127833; -.
DR GeneCards; SYT2; -.
DR HGNC; HGNC:11510; SYT2.
DR HPA; ENSG00000143858; Tissue enriched (brain).
DR MalaCards; SYT2; -.
DR MIM; 600104; gene.
DR MIM; 616040; phenotype.
DR MIM; 619461; phenotype.
DR neXtProt; NX_Q8N9I0; -.
DR OpenTargets; ENSG00000143858; -.
DR Orphanet; 98914; Presynaptic congenital myasthenic syndromes.
DR PharmGKB; PA36291; -.
DR VEuPathDB; HostDB:ENSG00000143858; -.
DR eggNOG; KOG1028; Eukaryota.
DR GeneTree; ENSGT00940000157586; -.
DR HOGENOM; CLU_023008_0_1_1; -.
DR InParanoid; Q8N9I0; -.
DR OMA; PMATMEN; -.
DR OrthoDB; 925064at2759; -.
DR PhylomeDB; Q8N9I0; -.
DR TreeFam; TF315600; -.
DR PathwayCommons; Q8N9I0; -.
DR Reactome; R-HSA-5250958; Toxicity of botulinum toxin type B (botB).
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; Q8N9I0; -.
DR SIGNOR; Q8N9I0; -.
DR BioGRID-ORCS; 127833; 13 hits in 1070 CRISPR screens.
DR ChiTaRS; SYT2; human.
DR GeneWiki; SYT2; -.
DR GenomeRNAi; 127833; -.
DR Pharos; Q8N9I0; Tbio.
DR PRO; PR:Q8N9I0; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8N9I0; protein.
DR Bgee; ENSG00000143858; Expressed in pons and 144 other tissues.
DR Genevisible; Q8N9I0; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IBA:GO_Central.
DR GO; GO:0042584; C:chromaffin granule membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0031045; C:dense core granule; IBA:GO_Central.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030672; C:synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; ISS:UniProtKB.
DR GO; GO:0030276; F:clathrin binding; IBA:GO_Central.
DR GO; GO:0043533; F:inositol 1,3,4,5 tetrakisphosphate binding; ISS:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central.
DR GO; GO:0000149; F:SNARE binding; IBA:GO_Central.
DR GO; GO:0019905; F:syntaxin binding; IBA:GO_Central.
DR GO; GO:0048791; P:calcium ion-regulated exocytosis of neurotransmitter; IBA:GO_Central.
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:1903861; P:positive regulation of dendrite extension; IDA:UniProtKB.
DR GO; GO:0017158; P:regulation of calcium ion-dependent exocytosis; IBA:GO_Central.
DR GO; GO:0014059; P:regulation of dopamine secretion; IBA:GO_Central.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; 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; IPR015428; Synaptotagmin1.
DR PANTHER; PTHR10024:SF223; PTHR10024:SF223; 1.
DR Pfam; PF00168; C2; 2.
DR PRINTS; PR00360; C2DOMAIN.
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 3D-structure; Calcium; Congenital myasthenic syndrome; Cytoplasmic vesicle;
KW Differentiation; Disease variant; Glycoprotein; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Synapse; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..419
FT /note="Synaptotagmin-2"
FT /id="PRO_0000183942"
FT TOPO_DOM 1..62
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 63..83
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 84..419
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 139..258
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 270..403
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 16..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 99..138
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 133..379
FT /note="Phospholipid binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 16..37
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 100..119
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 120..134
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 169
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 170
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 170
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 176
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 228
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 228
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 229
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 233
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 234
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 236
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 236
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 301
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 307
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 361
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 363
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 122
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P29101"
FT MOD_RES 125
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P46097"
FT MOD_RES 227
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P46097"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 269..419
FT /note="Missing (in CMS7B)"
FT /evidence="ECO:0000269|PubMed:32776697"
FT /id="VAR_086137"
FT VARIANT 307
FT /note="D -> A (in CMS7A; dbSNP:rs587777781)"
FT /evidence="ECO:0000269|PubMed:25192047"
FT /id="VAR_072578"
FT VARIANT 308
FT /note="P -> L (in CMS7A; dbSNP:rs587777782)"
FT /evidence="ECO:0000269|PubMed:25192047"
FT /id="VAR_072579"
FT VARIANT 309..419
FT /note="Missing (in CMS7B)"
FT /evidence="ECO:0000269|PubMed:32776697"
FT /id="VAR_086138"
FT VARIANT 361..365
FT /note="Missing (in CMS7A)"
FT /evidence="ECO:0000269|PubMed:33320396"
FT /id="VAR_086139"
FT VARIANT 365
FT /note="L -> P (in CMS7A)"
FT /evidence="ECO:0000269|PubMed:34037996"
FT /id="VAR_086140"
FT CONFLICT 310
FT /note="V -> G (in Ref. 1; BAC04354)"
FT /evidence="ECO:0000305"
FT HELIX 41..55
FT /evidence="ECO:0007829|PDB:6G5G"
SQ SEQUENCE 419 AA; 46872 MW; BE3855E9CDE2D76E CRC64;
MRNIFKRNQE PIVAPATTTA TMPIGPVDNS TESGGAGESQ EDMFAKLKEK LFNEINKIPL
PPWALIAIAV VAGLLLLTCC FCICKKCCCK KKKNKKEKGK GMKNAMNMKD MKGGQDDDDA
ETGLTEGEGE GEEEKEPENL GKLQFSLDYD FQANQLTVGV LQAAELPALD MGGTSDPYVK
VFLLPDKKKK YETKVHRKTL NPAFNETFTF KVPYQELGGK TLVMAIYDFD RFSKHDIIGE
VKVPMNTVDL GQPIEEWRDL QGGEKEEPEK LGDICTSLRY VPTAGKLTVC ILEAKNLKKM
DVGGLSDPYV KIHLMQNGKR LKKKKTTVKK KTLNPYFNES FSFEIPFEQI QKVQVVVTVL
DYDKLGKNEA IGKIFVGSNA TGTELRHWSD MLANPRRPIA QWHSLKPEEE VDALLGKNK
