ID SYT5_HUMAN Reviewed; 386 AA. AC O00445; B3KWJ8; B7Z300; Q86X72; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 11-JUL-2003, sequence version 2. DT 24-JAN-2024, entry version 197. DE RecName: Full=Synaptotagmin-5; DE AltName: Full=Synaptotagmin V; DE Short=SytV; GN Name=SYT5; 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 [GENOMIC DNA]. RC TISSUE=Brain; RX PubMed=9177789; DOI=10.1006/geno.1997.4722; RA Craxton M.A., Olsen A., Goedert M.; RT "Human synaptotagmin V (SYT5): sequence, genomic structure, and chromosomal RT location."; RL Genomics 42:165-169(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Caudate nucleus; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-111. RC TISSUE=Brain; 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 [5] {ECO:0007744|PDB:5H4Y, ECO:0007744|PDB:5H4Z} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 107-233 IN COMPLEX WITH CALCIUM, RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 105-233 OF MUTANT GLY-202 IN RP COMPLEX WITH CALCIUM, AND MUTAGENESIS OF SER-202. RX PubMed=27793683; DOI=10.1016/j.ijbiomac.2016.10.083; RA Qiu X., Ge J., Gao Y., Teng M., Niu L.; RT "Structural analysis of Ca2+-binding pocket of synaptotagmin 5 C2A RT domain."; RL Int. J. Biol. Macromol. 95:946-953(2017). CC -!- FUNCTION: May be involved in Ca(2+)-dependent exocytosis of secretory CC vesicles through Ca(2+) and phospholipid binding to the C2 domain or CC may serve as Ca(2+) sensors in the process of vesicular trafficking and CC exocytosis. Regulates the Ca(2+)-dependent secretion of norepinephrine CC in PC12 cells. Required for export from the endocytic recycling CC compartment to the cell surface (By similarity). {ECO:0000250}. CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00041, ECO:0000269|PubMed:27793683}; CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 CC domains. {ECO:0000269|PubMed:15057824}; CC -!- SUBUNIT: Homodimer (By similarity). Interacts with both alpha- and CC beta-tubulin (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:P47861}. CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic CC vesicle membrane {ECO:0000250}; Single-pass membrane protein CC {ECO:0000250}. Recycling endosome membrane {ECO:0000250}; Single-pass CC membrane protein {ECO:0000250}. Note=In mast cells, localizes to the CC endocytic recycling compartment. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O00445-1; Sequence=Displayed; CC Name=2; CC IsoId=O00445-2; Sequence=VSP_057177, VSP_057178; 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; X96783; CAA65579.1; -; Genomic_DNA. DR EMBL; AK125182; BAG54160.1; -; mRNA. DR EMBL; AK295337; BAH12036.1; -; mRNA. DR EMBL; AC010327; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC046157; AAH46157.1; -; mRNA. DR CCDS; CCDS12919.1; -. [O00445-1] DR CCDS; CCDS74455.1; -. [O00445-2] DR RefSeq; NP_001284703.1; NM_001297774.1. [O00445-2] DR RefSeq; NP_003171.2; NM_003180.2. [O00445-1] DR RefSeq; XP_006723402.1; XM_006723339.3. [O00445-1] DR RefSeq; XP_016882664.1; XM_017027175.1. [O00445-1] DR RefSeq; XP_016882665.1; XM_017027176.1. DR PDB; 5H4Y; X-ray; 1.90 A; A=102-242. DR PDB; 5H4Z; X-ray; 3.01 A; A/B=102-242. DR PDBsum; 5H4Y; -. DR PDBsum; 5H4Z; -. DR AlphaFoldDB; O00445; -. DR SMR; O00445; -. DR BioGRID; 112725; 11. DR ELM; O00445; -. DR IntAct; O00445; 9. DR MINT; O00445; -. DR STRING; 9606.ENSP00000346265; -. DR iPTMnet; O00445; -. DR PhosphoSitePlus; O00445; -. DR BioMuta; SYT5; -. DR jPOST; O00445; -. DR MassIVE; O00445; -. DR MaxQB; O00445; -. DR PaxDb; 9606-ENSP00000346265; -. DR PeptideAtlas; O00445; -. DR ProteomicsDB; 47896; -. [O00445-1] DR ProteomicsDB; 6480; -. DR Antibodypedia; 2420; 235 antibodies from 33 providers. DR DNASU; 6861; -. DR Ensembl; ENST00000354308.8; ENSP00000346265.2; ENSG00000129990.15. [O00445-1] DR Ensembl; ENST00000537500.5; ENSP00000442896.1; ENSG00000129990.15. [O00445-1] DR Ensembl; ENST00000590851.5; ENSP00000465576.1; ENSG00000129990.15. [O00445-2] DR GeneID; 6861; -. DR KEGG; hsa:6861; -. DR MANE-Select; ENST00000354308.8; ENSP00000346265.2; NM_003180.3; NP_003171.2. DR UCSC; uc002qjm.2; human. [O00445-1] DR AGR; HGNC:11513; -. DR CTD; 6861; -. DR DisGeNET; 6861; -. DR GeneCards; SYT5; -. DR HGNC; HGNC:11513; SYT5. DR HPA; ENSG00000129990; Group enriched (brain, pituitary gland). DR MIM; 600782; gene. DR neXtProt; NX_O00445; -. DR OpenTargets; ENSG00000129990; -. DR PharmGKB; PA36294; -. DR VEuPathDB; HostDB:ENSG00000129990; -. DR eggNOG; KOG1028; Eukaryota. DR GeneTree; ENSGT00940000161816; -. DR HOGENOM; CLU_023008_0_1_1; -. DR InParanoid; O00445; -. DR OMA; CLCRKRC; -. DR OrthoDB; 590187at2759; -. DR PhylomeDB; O00445; -. DR TreeFam; TF315600; -. DR PathwayCommons; O00445; -. DR Reactome; R-HSA-422356; Regulation of insulin secretion. DR SignaLink; O00445; -. DR BioGRID-ORCS; 6861; 30 hits in 1153 CRISPR screens. DR GeneWiki; SYT5; -. DR GenomeRNAi; 6861; -. DR Pharos; O00445; Tbio. DR PRO; PR:O00445; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; O00445; Protein. DR Bgee; ENSG00000129990; Expressed in cortical plate and 138 other cell types or tissues. DR ExpressionAtlas; O00445; baseline and differential. DR GO; GO:0030424; C:axon; IBA:GO_Central. DR GO; GO:0031045; C:dense core granule; IBA:GO_Central. DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0099012; C:neuronal dense core vesicle membrane; IEA:Ensembl. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:1990769; C:proximal neuron projection; IEA:Ensembl. DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0030672; C:synaptic vesicle membrane; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IBA:GO_Central. DR GO; GO:0030276; F:clathrin binding; IBA:GO_Central. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IEA:Ensembl. DR GO; GO:0001786; F:phosphatidylserine binding; IBA:GO_Central. DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl. 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:0071277; P:cellular response to calcium ion; IBA:GO_Central. DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc. 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; cd21342; Syt1_2_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:SF282; SYNAPTOTAGMIN-5; 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; O00445; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cytoplasmic vesicle; Endosome; KW Membrane; Metal-binding; Reference proteome; Repeat; Synapse; KW Transmembrane; Transmembrane helix. FT CHAIN 1..386 FT /note="Synaptotagmin-5" FT /id="PRO_0000183951" FT TOPO_DOM 1..24 FT /note="Vesicular" FT /evidence="ECO:0000255" FT TRANSMEM 25..45 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 46..386 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 108..227 FT /note="C2 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 239..372 FT /note="C2 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..17 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 138 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 139 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 139 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 145 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 197 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 197 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 198 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 199 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 199 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 199 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 202 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 205 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 205 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 270 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 276 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 330 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 332 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT VAR_SEQ 1..84 FT /note="MFPEPPTPGPPSPDTPPDSSRISHGPVPPWALATIVLVSGLLIFSCCFCLYR FT KSCRRRTGKKSQAQAQVHLQEVKGLGQSYIDK -> MTRGGCPVSARLFAQRPHGSWSS FT LLCVGLKGRLGWEWGTRVLECLCRKDSRTPPPCSRSPQPRGLHRPTRLPTPVASATAQ FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057177" FT VAR_SEQ 237 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057178" FT VARIANT 4 FT /note="E -> D (in dbSNP:rs2301279)" FT /id="VAR_052240" FT VARIANT 111 FT /note="R -> Q (in dbSNP:rs11542503)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334" FT /id="VAR_034528" FT MUTAGEN 202 FT /note="S->G: Does not affect Ca(2+) affinity as measured by FT isothermal titration calorimetry of the mutant protein." FT /evidence="ECO:0000269|PubMed:27793683" FT CONFLICT 24 FT /note="H -> R (in Ref. 2; BAG54160)" FT /evidence="ECO:0000305" FT STRAND 111..119 FT /evidence="ECO:0007829|PDB:5H4Y" FT TURN 120..123 FT /evidence="ECO:0007829|PDB:5H4Y" FT STRAND 124..134 FT /evidence="ECO:0007829|PDB:5H4Y" FT STRAND 146..153 FT /evidence="ECO:0007829|PDB:5H4Y" FT STRAND 157..161 FT /evidence="ECO:0007829|PDB:5H4Y" FT STRAND 172..180 FT /evidence="ECO:0007829|PDB:5H4Y" FT HELIX 183..188 FT /evidence="ECO:0007829|PDB:5H4Y" FT STRAND 190..197 FT /evidence="ECO:0007829|PDB:5H4Y" FT STRAND 200..202 FT /evidence="ECO:0007829|PDB:5H4Y" FT STRAND 205..213 FT /evidence="ECO:0007829|PDB:5H4Y" FT HELIX 214..216 FT /evidence="ECO:0007829|PDB:5H4Y" FT STRAND 223..228 FT /evidence="ECO:0007829|PDB:5H4Y" SQ SEQUENCE 386 AA; 42900 MW; 96A36792D177FD55 CRC64; MFPEPPTPGP PSPDTPPDSS RISHGPVPPW ALATIVLVSG LLIFSCCFCL YRKSCRRRTG KKSQAQAQVH LQEVKGLGQS YIDKVQPEVE ELEPAPSGPG QQVADKHELG RLQYSLDYDF QSGQLLVGIL QAMGLAALDL GGSSDPYVRV YLLPDKRRRY ETKVHRQTLN PHFGETFAFK VPYVELGGRV LVMAVYDFDR FSRNDAIGEV RVPMSSVDLG RPVQAWRELQ AAPREEQEKL GDICFSLRYV PTAGKLTVIV LEAKNLKKMD VGGLSDPYVK VHLLQGGKKV RKKKTTIKKN TLNPYYNEAF SFEVPCDQVQ KVQVELTVLD YDKLGKNEAI GRVAVGAAAG GAGLRHWADM LANPRRPIAQ WHSLRPPDRV RLLPAP //