UN13A_MOUSE
ID UN13A_MOUSE Reviewed; 1712 AA.
AC Q4KUS2; E9QKH9; Q3UHG2;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Protein unc-13 homolog A {ECO:0000305};
DE AltName: Full=Munc13-1 {ECO:0000303|PubMed:23229896};
GN Name=Unc13a {ECO:0000312|MGI:MGI:3051532};
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] {ECO:0000312|EMBL:AAX09281.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:AAX09281.1};
RA Wang X., Honsbein A., Kilimann M.W.;
RT "Mouse Munc13-1 sequence.";
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAE27895.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 127-1712.
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE27895.1};
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 [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10440375; DOI=10.1038/22768;
RA Augustin I., Rosenmund C., Suedhof T.C., Brose N.;
RT "Munc13-1 is essential for fusion competence of glutamatergic synaptic
RT vesicles.";
RL Nature 400:457-461(1999).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=12070347; DOI=10.1073/pnas.122623799;
RA Varoqueaux F., Sigler A., Rhee J.-S., Brose N., Enk C., Reim K.,
RA Rosenmund C.;
RT "Total arrest of spontaneous and evoked synaptic transmission but normal
RT synaptogenesis in the absence of Munc13-mediated vesicle priming.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:9037-9042(2002).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=15988013; DOI=10.1128/mcb.25.14.5973-5984.2005;
RA Varoqueaux F., Sons M.S., Plomp J.J., Brose N.;
RT "Aberrant morphology and residual transmitter release at the Munc13-
RT deficient mouse neuromuscular synapse.";
RL Mol. Cell. Biol. 25:5973-5984(2005).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=16697276; DOI=10.1016/j.cmet.2006.04.012;
RA Kang L., He Z., Xu P., Fan J., Betz A., Brose N., Xu T.;
RT "Munc13-1 is required for the sustained release of insulin from pancreatic
RT beta cells.";
RL Cell Metab. 3:463-468(2006).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=16644700; DOI=10.2337/db05-1263;
RA Kwan E.P., Xie L., Sheu L., Nolan C.J., Prentki M., Betz A., Brose N.,
RA Gaisano H.Y.;
RT "Munc13-1 deficiency reduces insulin secretion and causes abnormal glucose
RT tolerance.";
RL Diabetes 55:1421-1429(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [10] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF HIS-563.
RX PubMed=17267576; DOI=10.1523/jneurosci.4908-06.2007;
RA Basu J., Betz A., Brose N., Rosenmund C.;
RT "Munc13-1 C1 domain activation lowers the energy barrier for synaptic
RT vesicle fusion.";
RL J. Neurosci. 27:1200-1210(2007).
RN [11] {ECO:0000305}
RP FUNCTION.
RX PubMed=17639022; DOI=10.2337/db06-1207;
RA Kwan E.P., Xie L., Sheu L., Ohtsuka T., Gaisano H.Y.;
RT "Interaction between Munc13-1 and RIM is critical for glucagon-like
RT peptide-1 mediated rescue of exocytotic defects in Munc13-1 deficient
RT pancreatic beta-cells.";
RL Diabetes 56:2579-2588(2007).
RN [12]
RP IDENTIFICATION BY 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 [13]
RP INTERACTION WITH FBXO45.
RX PubMed=19996097; DOI=10.1074/jbc.m109.046284;
RA Tada H., Okano H.J., Takagi H., Shibata S., Yao I., Matsumoto M., Saiga T.,
RA Nakayama K.I., Kashima H., Takahashi T., Setou M., Okano H.;
RT "Fbxo45, a novel ubiquitin ligase, regulates synaptic activity.";
RL J. Biol. Chem. 285:3840-3849(2010).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23229896; DOI=10.1083/jcb.201208024;
RA van de Bospoort R., Farina M., Schmitz S.K., de Jong A., de Wit H.,
RA Verhage M., Toonen R.F.;
RT "Munc13 controls the location and efficiency of dense-core vesicle release
RT in neurons.";
RL J. Cell Biol. 199:883-891(2012).
CC -!- FUNCTION: Plays a role in vesicle maturation during exocytosis as a
CC target of the diacylglycerol second messenger pathway. Involved in
CC neurotransmitter release by acting in synaptic vesicle priming prior to
CC vesicle fusion and participates in the activity-dependent refilling of
CC readily releasable vesicle pool (RRP). Essential for synaptic vesicle
CC maturation in most excitatory/glutamatergic but not inhibitory/GABA-
CC mediated synapses. Facilitates neuronal dense core vesicles fusion as
CC well as controls the location and efficiency of their synaptic release
CC (PubMed:23229896). Also involved in secretory granule priming in
CC insulin secretion. Plays a role in dendrite formation by melanocytes
CC (By similarity). {ECO:0000250|UniProtKB:Q62768,
CC ECO:0000250|UniProtKB:Q9UPW8, ECO:0000269|PubMed:10440375,
CC ECO:0000269|PubMed:12070347, ECO:0000269|PubMed:15988013,
CC ECO:0000269|PubMed:16644700, ECO:0000269|PubMed:16697276,
CC ECO:0000269|PubMed:17267576, ECO:0000269|PubMed:17639022,
CC ECO:0000269|PubMed:23229896}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with the N-termini of STX1A and/or STX1B1 and DOC2A.
CC Interacts with BSN. Interacts with RIMS1 which recruits UNC13A to the
CC active zone. Forms homodimers via its first C2 domain. Also interacts
CC via this domain with the zinc finger domain of RIMS2. Part of a complex
CC consisting of ERC2, RIMS1 and UNC13A. Also part of a complex consisting
CC of UNC13A, RIMS2 and RAB3A (By similarity). Interacts with FBXO45 (via
CC SRY domain); leading to the degradation of UNC13A by the proteasome
CC (PubMed:19996097). {ECO:0000250|UniProtKB:Q62768,
CC ECO:0000269|PubMed:19996097}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q62768}. Cell
CC membrane {ECO:0000250|UniProtKB:Q62768}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q62768}. Presynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q62768}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q62768}. Presynaptic active zone
CC {ECO:0000305|PubMed:23229896}. Note=Translocated to the plasma membrane
CC in response to phorbol ester binding. {ECO:0000250|UniProtKB:Q62768}.
CC -!- DOMAIN: The C2 domains are not involved in calcium-dependent
CC phospholipid binding. {ECO:0000250|UniProtKB:Q62768}.
CC -!- DOMAIN: The C-terminal region containing both MHD domains and the third
CC C2 domain is required for synaptic vesicle priming activity.
CC {ECO:0000250|UniProtKB:Q62768}.
CC -!- DISRUPTION PHENOTYPE: Mice display normal synapse formation but
CC abnormal synaptic vesicle maturation and die shortly after birth.
CC Heterozygotes exhibit impaired insulin secretion and abnormal glucose
CC tolerance. {ECO:0000269|PubMed:10440375}.
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; AY753536; AAX09281.1; -; mRNA.
DR EMBL; AC162033; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK147408; BAE27895.1; -; mRNA.
DR CCDS; CCDS22402.2; -.
DR RefSeq; NP_001025044.2; NM_001029873.2.
DR PDB; 7T7C; EM; 10.00 A; A/B/C/D/E/F/G/H/I/J/K/L=525-656, A/B/C/D/E/F/G/H/I/J/K/L=1448-1712.
DR PDB; 7T7R; EM; 10.00 A; A/B/C=525-1403, A/B/C=1448-1712.
DR PDB; 7T7V; EM; 10.00 A; A=525-1403, A=1448-1712.
DR PDB; 7T7X; EM; 10.00 A; A=752-1396, A=1643-1712.
DR PDB; 7T81; EM; 10.00 A; A/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y=752-1396, A/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y=1643-1712.
DR PDBsum; 7T7C; -.
DR PDBsum; 7T7R; -.
DR PDBsum; 7T7V; -.
DR PDBsum; 7T7X; -.
DR PDBsum; 7T81; -.
DR AlphaFoldDB; Q4KUS2; -.
DR BMRB; Q4KUS2; -.
DR SMR; Q4KUS2; -.
DR BioGRID; 238191; 3.
DR IntAct; Q4KUS2; 4.
DR MINT; Q4KUS2; -.
DR STRING; 10090.ENSMUSP00000030170; -.
DR iPTMnet; Q4KUS2; -.
DR PhosphoSitePlus; Q4KUS2; -.
DR SwissPalm; Q4KUS2; -.
DR MaxQB; Q4KUS2; -.
DR PaxDb; Q4KUS2; -.
DR PeptideAtlas; Q4KUS2; -.
DR PRIDE; Q4KUS2; -.
DR ProteomicsDB; 300080; -.
DR Antibodypedia; 43803; 33 antibodies from 18 providers.
DR DNASU; 382018; -.
DR Ensembl; ENSMUST00000030170; ENSMUSP00000030170; ENSMUSG00000034799.
DR GeneID; 382018; -.
DR KEGG; mmu:382018; -.
DR UCSC; uc033jgb.1; mouse.
DR CTD; 23025; -.
DR MGI; MGI:3051532; Unc13a.
DR VEuPathDB; HostDB:ENSMUSG00000034799; -.
DR eggNOG; KOG1011; Eukaryota.
DR GeneTree; ENSGT00940000161905; -.
DR HOGENOM; CLU_001304_3_0_1; -.
DR InParanoid; Q4KUS2; -.
DR OMA; SFQGSEF; -.
DR OrthoDB; 117172at2759; -.
DR TreeFam; TF312844; -.
DR BioGRID-ORCS; 382018; 5 hits in 74 CRISPR screens.
DR ChiTaRS; Unc13a; mouse.
DR PRO; PR:Q4KUS2; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q4KUS2; protein.
DR Bgee; ENSMUSG00000034799; Expressed in superior frontal gyrus and 96 other tissues.
DR ExpressionAtlas; Q4KUS2; baseline and differential.
DR Genevisible; Q4KUS2; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0044305; C:calyx of Held; IDA:ParkinsonsUK-UCL.
DR GO; GO:0060076; C:excitatory synapse; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005798; C:Golgi-associated vesicle; ISO:MGI.
DR GO; GO:0031594; C:neuromuscular junction; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; ISS:ParkinsonsUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098793; C:presynapse; IDA:MGI.
DR GO; GO:0048786; C:presynaptic active zone; IDA:ParkinsonsUK-UCL.
DR GO; GO:0098831; C:presynaptic active zone cytoplasmic component; ISO:MGI.
DR GO; GO:0042734; C:presynaptic membrane; ISS:ParkinsonsUK-UCL.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0097060; C:synaptic membrane; ISO:MGI.
DR GO; GO:0030672; C:synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0043195; C:terminal bouton; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005516; F:calmodulin binding; ISO:MGI.
DR GO; GO:0019992; F:diacylglycerol binding; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0000149; F:SNARE binding; ISO:MGI.
DR GO; GO:0030507; F:spectrin binding; ISO:MGI.
DR GO; GO:0019905; F:syntaxin binding; ISO:MGI.
DR GO; GO:0017075; F:syntaxin-1 binding; ISS:ParkinsonsUK-UCL.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0061789; P:dense core granule priming; ISO:MGI.
DR GO; GO:0060384; P:innervation; IGI:MGI.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISO:MGI.
DR GO; GO:0007528; P:neuromuscular junction development; IGI:MGI.
DR GO; GO:0099011; P:neuronal dense core vesicle exocytosis; IMP:UniProtKB.
DR GO; GO:0007269; P:neurotransmitter secretion; IMP:MGI.
DR GO; GO:1903861; P:positive regulation of dendrite extension; ISO:MGI.
DR GO; GO:1900451; P:positive regulation of glutamate receptor signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0001956; P:positive regulation of neurotransmitter secretion; IMP:MGI.
DR GO; GO:0031915; P:positive regulation of synaptic plasticity; IGI:ParkinsonsUK-UCL.
DR GO; GO:0099525; P:presynaptic dense core vesicle exocytosis; IGI:SynGO.
DR GO; GO:1902991; P:regulation of amyloid precursor protein catabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0048172; P:regulation of short-term neuronal synaptic plasticity; IMP:MGI.
DR GO; GO:0010807; P:regulation of synaptic vesicle priming; ISO:MGI.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IMP:MGI.
DR GO; GO:0016081; P:synaptic vesicle docking; IGI:MGI.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; IDA:SynGO.
DR GO; GO:0016188; P:synaptic vesicle maturation; IMP:MGI.
DR GO; GO:0016082; P:synaptic vesicle priming; IMP:ParkinsonsUK-UCL.
DR CDD; cd00029; C1; 1.
DR CDD; cd04027; C2B_Munc13; 1.
DR Gene3D; 2.60.40.150; -; 3.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR010439; MUN_dom.
DR InterPro; IPR014770; Munc13_1.
DR InterPro; IPR014772; Munc13_dom-2.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR027080; Unc-13.
DR InterPro; IPR037302; Unc-13_C2B.
DR InterPro; IPR027082; Unc13A.
DR PANTHER; PTHR10480; PTHR10480; 1.
DR PANTHER; PTHR10480:SF1; PTHR10480:SF1; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00168; C2; 3.
DR Pfam; PF06292; MUN; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00239; C2; 3.
DR SMART; SM01145; DUF1041; 1.
DR SUPFAM; SSF49562; SSF49562; 3.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS50004; C2; 3.
DR PROSITE; PS51258; MHD1; 1.
DR PROSITE; PS51259; MHD2; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell membrane; Cell projection; Coiled coil;
KW Cytoplasm; Differentiation; Exocytosis; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Synapse; Zinc; Zinc-finger.
FT CHAIN 1..1712
FT /note="Protein unc-13 homolog A"
FT /id="PRO_0000306285"
FT DOMAIN 1..97
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 668..792
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1102..1245
FT /note="MHD1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00587"
FT DOMAIN 1354..1521
FT /note="MHD2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00588"
FT DOMAIN 1535..1662
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT ZN_FING 562..612
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 185..454
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 321..360
FT /evidence="ECO:0000255"
FT COMPBIAS 203..224
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 253..276
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 277..317
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 318..365
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 418..451
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 576
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q62768"
FT BINDING 579
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q62768"
FT BINDING 593
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q62768"
FT BINDING 596
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q62768"
FT BINDING 604
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q62768"
FT BINDING 612
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q62768"
FT BINDING 701
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 701
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 707
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 753
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 753
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 755
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 755
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 772
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62768"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62768"
FT MOD_RES 244
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62768"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62768"
FT MUTAGEN 563
FT /note="H->V: Reduces number of fusion-competent vesicles in
FT neurons."
FT /evidence="ECO:0000269|PubMed:17267576"
FT CONFLICT 127
FT /note="F -> I (in Ref. 3; BAE27895)"
FT /evidence="ECO:0000305"
FT CONFLICT 479
FT /note="D -> E (in Ref. 1; AAX09281)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1712 AA; 193782 MW; AA498D15557454EC CRC64;
MSLLCVGVKK AKFDGAQEKF NTYVTLKVQN VKSTTIAVRG SQPSWEQDFM FEINRLDLGL
TVEVWNKGLI WDTMVGTVWI PLRTIRQSNE EGPGEWLTLD SQAIMADSEI CGTKDPTFHR
ILLDAHFELP LDIPEEEARY WAKKLEQLNA MRDQDEYSFQ DQQDKPLPVP SSQCCNWNYF
GWGEQNDDPD SAVDDRDSDY RSETSNSIPP PYYTTSQPNA SVHQYSVRPP PLGSRESYSD
SMHSYEEFSE PRALSPTGSS RYASSGELSQ GSSQLSEDFD PDEHSLQGSE LDDERDRDSY
HSCHSSVSYH KDSPRWDQDD EDLEDLEDLE DEELPEEEEE LEEEGEEELE EEDLEEEEEV
PDDLASYTQQ EDTTVAEPKE FKRISFPTAA PQKDDKVSAV PTEAPEVAKG IPKAATPEEK
AAAERAQEAE PPKSEESFRS REEEEGQEGQ DAMSRAKANW LRAFNKVRMQ LQEARGEGDM
SKSLWFKGGP GGGLIIIDSM PDIRKRKPIP LVSDLAMSLV QSRKAGITSA LASSTLNNEE
LKNHVYKKTL QALIYPISCT TPHNFEVWTA TTPTYCYECE GLLWGIARQG MRCTECGVKC
HEKCQDLLNA DCLQRAAEKS SKHGAEDRTQ NIIMVLKDRM KIRERNKPEI FELIQEIFAV
TKSAHTQQMK AVKQSVLDGT SKWSAKISIT VVCAQGLQAK DKTGSSDPYV TVQVGKTKKR
TKTIYGNLNP VWEENFHFEC HNSSDRIKVR VWDEDDDIKS RVKQRFKRES DDFLGQTIIE
VRTLSGEMDV WYNLDKRTDK SAVSGAIRLH ISVEIKGEEK VAPYHVQYTC LHENLFHFVT
DVQNNGVVKI PDAKGDDAWK VYYDETAQEI VDEFAMRYGV ESIYQAMTHF ACLSSKYMCP
GVPAVMSTLL ANINAYYAHT TASTNVSASD RFAASNFGKE RFVKLLDQLH NSLRIDLSMY
RNNFPASSPE RLQDLKSTVD LLTSITFFRM KVQELQSPPR ASQVVKDCVK ACLNSTYEYI
FNNCHELYGR EYQTDPAKKG EVPPEEQGPS IKNLDFWSKL ITLIVSIIEE DKNSYTPCLN
QFPQELNVGK ISAEVMWSLF AQDMKYAMEE HDKHRLCKSA DYMNLHFKVK WLYNEYVAEL
PTFKDRVPEY PAWFEPFVIQ WLDENEEVSR DFLHGALERD KKDGFQQTSE HALFSCSVVD
VFSQLNQSFE IIKKLECPDP QIVGHYMRRF AKTISNVLLQ YADIVSKDFA SYCSKEKEKV
PCILMNNTQQ LRVQLEKMFE AMGGKELDAE ASGTLKELQV KLNNVLDELS HVFATSFQPH
IEECVRQMGD ILSQVKGTGN VPASACSSVA QDADNVLQPI MDLLDSNLTL FAKICEKTVL
KRVLKELWKL VMNTMEKTIV LPPLTDQTMI GTLLRKHGKG LEKGRVKLPS HSDGTQMIFN
AAKELGQLSK LKDHMVREEA KSLTPKQCAV VELALDTIKQ YFHAGGVGLK KTFLEKSPDL
QSLRYALSLY TQATDLLIKT FVQTQSAQGS GVEDPVGEVS VHVELFTHPG TGEQKVTVKV
VAANDLKWQT SGIFRPFIEV NIVGPQLSDK KRKFATKSKN NSWAPKYNES FQFSLSADAG
PECYELQVCV KDYCFAREDR TVGLAVLQLR ELAQRGSAAC WLPLGRRIHM DDTGLTVLRI
LSQRSNDEVA KEFVKLKSDT RSAEEGGAAP AP
