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 24-JAN-2024, entry version 180. 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; Evidence={ECO:0000255|PROSITE- CC 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). Heterodimer; heterodimerizes with CC SYT1 in presence of calcium (By similarity). Interacts with STON2 CC (PubMed:11381094). Interacts with SCAMP5 (PubMed:19234194). Interacts CC with PRRT2 (By similarity). {ECO:0000250|UniProtKB:P29101, CC ECO:0000250|UniProtKB:P46097, ECO:0000269|PubMed:11381094, CC 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; Q9C0I4: THSD7B; NbExp=3; IntAct=EBI-8032987, EBI-311394; 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|UniProtKB:P29101}; Single-pass membrane CC protein {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle, CC chromaffin granule membrane {ECO:0000250|UniProtKB:P21707}; Single-pass CC membrane protein {ECO:0000250|UniProtKB:P29101}. Cytoplasm CC {ECO:0000250|UniProtKB:P29101}. 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 -!- PTM: Phosphorylation at Thr-199 by WNK1, changes the calcium CC requirement for SYT2-binding to phospholipid membranes. CC {ECO:0000250|UniProtKB:P29101}. 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}. 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; 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; 32. DR MINT; Q8N9I0; -. DR STRING; 9606.ENSP00000356237; -. DR DrugBank; DB00042; Botulinum toxin type B. DR GlyCosmos; Q8N9I0; 1 site, No reported glycans. DR GlyGen; Q8N9I0; 1 site. DR iPTMnet; Q8N9I0; -. DR PhosphoSitePlus; Q8N9I0; -. DR SwissPalm; Q8N9I0; -. DR BioMuta; SYT2; -. DR DMDM; 116242811; -. DR EPD; Q8N9I0; -. DR jPOST; Q8N9I0; -. DR MassIVE; Q8N9I0; -. DR PaxDb; 9606-ENSP00000356236; -. DR PeptideAtlas; Q8N9I0; -. DR ProteomicsDB; 72541; -. DR Antibodypedia; 34528; 308 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 AGR; HGNC:11510; -. 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; MPMTTME; -. DR OrthoDB; 590187at2759; -. 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 1154 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 145 other cell types or tissues. 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: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:0019905; F:syntaxin binding; IBA:GO_Central. DR GO; GO:0048791; P:calcium ion-regulated exocytosis of neurotransmitter; 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 CDD; cd08385; C2A_Synaptotagmin-1-5-6-9-10; 1. DR CDD; cd08402; C2B_Synaptotagmin-1; 1. DR CDD; cd21964; Syt2_N; 1. DR Gene3D; 2.60.40.150; C2 domain; 2. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR001565; Synaptotagmin. DR PANTHER; PTHR10024; SYNAPTOTAGMIN; 1. DR PANTHER; PTHR10024:SF223; SYNAPTOTAGMIN-2; 1. DR Pfam; PF00168; C2; 2. DR PRINTS; PR00360; C2DOMAIN. DR PRINTS; PR00399; SYNAPTOTAGMN. DR SMART; SM00239; C2; 2. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 2. DR PROSITE; PS50004; C2; 2. DR Genevisible; Q8N9I0; HS. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Congenital myasthenic syndrome; Cytoplasm; KW Cytoplasmic vesicle; Differentiation; Disease variant; Glycoprotein; KW Membrane; Metal-binding; Phosphoprotein; Reference proteome; Repeat; KW Synapse; Transmembrane; 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 199 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P29101" FT MOD_RES 227 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P46097" FT MOD_RES 383 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P29101" 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 //